Phenomap legend:
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Clear genotype related differences
Legend:
Subtle findings
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No significant differences
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Not analyzed
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Data is still in preparation
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Mutant projectGeneMuation typeViabilityFertilityBone &
Cartilage
BehaviourNeurologyEye &
Vision
Energy
Metabolism
Clinical
Chemistry
Immun-
ology
Cardio-
vascular
PathologyBodyweightReport
Dis3 / HEPD0659_5_E08-tm1bDis3Targeted mutationHomozygous - Lethal
Viability:
Homozygous - Lethal

Wildtype Heterozygote Homozygote Total
Male and female pubs born 10 18 0 28
Male pubs born 8 10 0 18
Female pubs born 2 8 0 10

Fertility:
Male gross findings: "
Female gross findings:

Primary Male screen Female screen
Total matings
Total pups born
Total litters
Bone & Cartilage

Summary:

Normal morphology and X-ray parameters in HET mice.




Behaviour

Summary:

There were no major genotype effects on prepulse inhibition and open field was not analysed
in these mice.




Neurology

Summary:

No difference at ABR.




Eye & Vision

Summary:

The Dis3 mutant mice show decreased retinal thickness. Lens development was not affected.




Energy Metabolism

Summary:

Body mass was reduced. No obvious effect on metabolic rate but mice were hyperactive.




Clinical Chemistry

Summary:

IpGTT: Slightly elevated basal glucose levels only in males and trend towards higher AUC values
predominantly in male mutants.

Insulin: No clear evidence of genotype-related differences.

Clinical Chemistry:
Slightly increased plasma ALP activity in both, female and male mutants, and decreased urea levels
in male mutants only.

Hematology: Small trends towards lower MCHC, MPV, PDW and P-LCR
in mutants.




Cardiovascular

Summary:

No alterations found by echocardiography.

ECG was performed and only minor changes of unclear
relevance were found. Increased QT dispersion and QTc dis in males.

No major effects
on the cardiovascular system could be detected.




Pathology

Summary:

LacZ expression was detected in brain except cerebellum and in the skin. Weak staining was
found in pancreas and kidney.

No statistically significant differences in absolute and normalized heart
weight between mutant and control mice.

Body weight is statistically significantly decreased in mutant
mice.

Histological examination using light microscopy did not reveal any pathological changes that could
be attributed to the genotype of the mice.



Discussion:

Histological examination using light microscopy did not reveal any pathological changes that could be attributed
to the genotype of the mice.

Bodyweight
Mocs2 / EPD0560_5_C09-tm1bMocs2Targeted mutationHomozygous - Lethal
Viability:
Homozygous - Lethal

Wildtype Heterozygote Homozygote Total
Male and female pubs born 16 19 0 35
Male pubs born 7 8 0 15
Female pubs born 9 11 0 20

Fertility:
Male gross findings: "
Female gross findings:

Primary Male screen Female screen
Total matings
Total pups born
Total litters
Bone & Cartilage

Summary:

In the primary screening no genotype-specific differences were found between mutants and controls.




Behaviour

Summary:

There was increased locomotor activity in the female mutant mice with the opposite effect in
the males. There was also a clear increase in prepulse inhibition responding.




Neurology

Summary:

No relevant difference in SHIRPA, grip and rotarod. Males were slightly heavier and performed subtly
worse in tests. ABR thresholds were slightly decreased for higher frequencies.




Eye & Vision

Summary:

We did not find ocular irregularities.




Energy Metabolism

Summary:

Body mass was increased and the resting metabolic rate decreased. Slight hypophagia was observed during
indirect calorimetry.




Clinical Chemistry

Summary:

IpGTT: No clearly genotype related effects, but trend to increased variability in mutants with more
mice showing elevated basal glucose or AUC values mainly in males.

Clinical chemistry: Mild
decrease in sodium, creatinine, calcium (phosphate in males), trend to increased albumin level and ALP
activity.

Hematological data did not provide clear evidence of genotype effects.

Taken together
we found mild genotype-related differences of unclear relevance. Differences seen in sodium, calcium and ALP
could indicate effects on water balance, mineral and bone metabolism.




Immunology

Summary:

The flow cytometry procedure was not performed.




Cardiovascular

Summary:

By echocardiography, a reduced systolic left ventricular posterior wall width and reduced heart rate was
observed in male mutants. Further, increased systolic left ventriuclar dimension, left ventricular volume and stroke
volume were observed in mutants and might indicate a mild hypertrophy.




Pathology

Summary:

LacZ expression is observed in brain (glial cells, cerebellum: Purkinje cells, Nucl. Dentatus); Spinal Cord
(grey matter, ventral columns, spinal ganglia) and Testis (patchy exprtession in tubuli seminiferi and possibly
Leydig cells).

Mutant mice showed increased total heart weights (Wilcoxon test: p<0.05) that may
be associated to their increased body size (tibia length) when compared to controls. Histological analysis
revealed no morphological correlation.



Discussion:

Mutant mice showed increased total heart weights (Wilcoxon test: p<0.05) that may be associated to
their increased body size (tibia length) when compared with the controls. Histological analysis revealed no
morphological correlation.

'Clear cell change' of thyroid epithelium in mutant mice is as yet
of unknown pathogenesis.

Bodyweight
Ivd / HEPD0535_3_F08-tm1bIvdTargeted mutationHomozygous - Lethal
Viability:
Homozygous - Lethal

Wildtype Heterozygote Homozygote Total
Male and female pubs born 17 36 0 53
Male pubs born 10 15 0 25
Female pubs born 7 21 0 28

Fertility:
Male gross findings: "
Female gross findings:

Primary Male screen Female screen
Total matings
Total pups born
Total litters
Bone & Cartilage

Summary:

In the analysis for dysmorphology, bone and cartilage, we did not detect any alterations.




Behaviour

Summary:

There was a subtle increase in centre distance by the female mutant mice and no
clear differences in prepulse inhibition.




Neurology

Summary:

No difference at ABR.




Eye & Vision

Summary:

No eye phenotype for the Ivd mouse mutants. OCT, scheimpflug and eye morphology showed comparable
phenotype read-outs to the control mice.




Clinical Chemistry

Summary:

Clinical chemistry: No evidence of clearly genotype related differences. Trend towards lowered chloride levels likely
by chance.

Hematology: No evidence of genotype-related differences. One male mutant animal (30298191) with
low RBC, HGB, HCT and high WBC and PLT values.

IpGTT: Increased body mass
loss in male mutants due to food withdrawal. Increased basal fasting glucose levels, No genotype-effects
on AUC values.




Cardiovascular

Summary:

No alterations were found by echocardiography.

By electraocardiography, increased QTc and ST interval durations
in females were found. This may provide an indication of arrythmias and of myocardial oxogen
supply/demand mismatch.

In addition, reduced mean SR and R amplitudes in males were found
with unknown relevance in cardiac function.



Discussion:

QT dispersion is defined as the difference between the longest and the shortest QT intervals.
Since the QT interval may vary according to the heart rate, it was corrected for
the heart rate (QTc).

Difficulties can arise in measuring the QT and ST intervals
when the morphology of the T-wave is abnormal, what is regularly observed in mice due
to the fast heart beat.

Changes in R and SR amplitudes were found between
groups of mice, which may indicate myocardial injury. But, since the ECgenie detects signals passively
through the paws, changes in the amplitude of signals should be viewed with caution.

Pathology

Summary:

LacZ expression is observed within salivary glands, stomach, intestine, pancreas, brain (neuronal layers), heart (auricles,
epicardium, vessel trunks), subcutis, testis, seminal vesicles, pituitary gland, trachea, lung (bronchi, bronchioli), kidney, uterus,
mesometrium, and urinary bladder.

Both, male and female heterozygous mice showed 'clear cell change'
of thyroid follicle epithelium that could not be observed in wildtype controls.

The clear
cell change in thyroid follicle epithelium cells is as yet of unknown pathogenesis but ballooning
of mitochondria, accumulation of lipid or glycogen or depositions of intracellular thyroglobulin may be possible
etiologies.



Discussion:

The clear cell change in thyroid follicle epithelium cells is as yet of unknown pathogenesis
but ballooning of mitochondria, accumulation of lipid or glycogen or depositions of intracellular thyroglobulin may
be possible etiologies.

Bodyweight
Cdkal1 / EPD0635_1_F06-tm1bCdkal1Targeted mutationHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pubs born 19 28 12 59
Male pubs born 9 18 8 35
Female pubs born 10 10 4 24
M: Fertile
F: Fertile
Fertility:
Male gross findings: Fertile"
Female gross findings: Fertile

Primary Male screen Female screen
Total matings 3 2
Total pups born 15 11
Total litters 3 2
Bone & Cartilage

Summary:

In the DXA analysis, we detected a significantly decreased body weight and fat mass in
males compared to controls.




Behaviour

Summary:

There was a subtle decrease in centre time and centre distance in the mutant mice
in the open field.




Neurology

Summary:

We detected no differences at SHIRPA, grip strength or rotarod. ABR thresholds of females were
increased for 12 and 18 kHz, but opposite in males without clear pattern.




Eye & Vision

Summary:

The eye tests were not performed.




Energy Metabolism

Summary:

No clear effects on energy turnover could be detected. Resting metabolic rate trended to be
decreased. Activity was decreased in male mutants.




Clinical Chemistry

Summary:

IpGTT: We found increased body mass loss due to food withdrawal and a trend towards
higher AUC values in mutants. However, only 4 mutant females were tested.

Clinical chemistry:
Slightly decreased cholesterol and triglycerides in both sexes and HDL and phosphate in males. Trend
to higher urea values in females.

Hematology: Slightly increased white blood cell counts in
male mutants.

Insulin: No evidence of genotype-related effects.




Immunology

Summary:

We found a slightly higher frequency of CD4+CD8- cells, together with a slightly lower frequency
of CD4-CD8+ cells within the T cell compartment of spleens from CDKAL1 mutant compared to wildtype controls
measured on the same day.




Cardiovascular

Summary:

Only mild genotype-related differences without relevance for the cardiovascular system were found:

Increased mean
SR and mean R amplitudes. Increased respiration rate.

Thus, the screening did not uncover
a cardiovascular phenotype.




Pathology

Summary:

No genotype associated LacZ expression was observed.

Male mutant mice showed a genotype-associated decrease
of body weight.

No statistically significant difference of total and normalized heart weight was
detected comparing mutant and control mice.

Histological examination using light microscopy did not reveal
any pathological changes that could be attributed to the genome of the mice.



Discussion:

Histological examination using light microscopy did not reveal any pathological changes that could be attributed
to the genome of the mice.

The cause of the reduced body weight in
male mutant mice remains to be elucidated.

Bodyweight
Wsb2 / HEPD0508_2_A11-tm1bWsb2Targeted mutationHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pubs born 8 27 5 40
Male pubs born 4 17 3 24
Female pubs born 4 10 2 16
M: Infertile
F: Infertile
Fertility:
Male gross findings: Infertile"
Female gross findings: Infertile

Primary Male screen Female screen
Total matings 2 2
Total pups born 0 0
Total litters 0 0
Bone & Cartilage

Summary:

In the morphological investigation via visual inspection, the upper teeth appearence was abnormal in most
of the mutants. In the DXA analysis we detected a significantly decreased BMC in males.
Concurrently body weight and fat mass were decreased in mutants (males).



Discussion:

The Wsb2 mutant mouse line was analyzed in the Dysmorphology, Bone and Cartilage module of
the German Mouse Clinic. In the morphological investigation via visual inspection, the upper teeth appearence was
abnormal in most of the mutants. In the DXA analysis we detected a significantly decreased
BMC in males. Concurrently body weight and fat mass (males) were decreased in mutants. The
decreased BMC in males is probably a secondary effect due to the differences in body
weight.

Behaviour

Summary:

The mutant mice showed decreased rearing activity in the open field and decreased acoustic reactivity.





Neurology

Summary:

Mutants showed more tail elevation and were quite strong given the huge body mass difference.
ABR showed no differences. Rotarod in a few animals was inconspicuous.




Eye & Vision

Summary:

We found thinner retinae and a reduced number of fundic main blood vessels.




Energy Metabolism

Summary:

Mutant mice showed reduced body mass throughout the whole phenotyping pipeline. During indirect calorimetry mice
showed very low food intake therefore genotype related effects on energy turnover may be secondary
to the fasting state.




Clinical Chemistry

Summary:

In the IpGTT we saw no clear genotype effect. However, only 3 female mutants were
tested, the rest was not analyzed for welfare reasons due to their low body mass.
In those females tested there was a trend towards lower basal glucose level and higher
AUC values in mutants.

Mutant animals show increased plasma potassium, chloride and iron levels,
clearly elevated ALP activity and slightly higher ALAT and ASAT activities in plasma compared to
controls. Glucose values and phosphate concentration in males tend to be lower in mutants, while
albumin, urea, bilirubin and fructosamin in males show a trend towards higher levels in mutants
compared to controls. The differences found could indicate a shift of acid-base balance towards acidosis
and effects on electrolyte balance, possibly due to changes in renal function, and might also
hint towards impaired liver function and/or integrity in mutant animals or effects on bone metabolism.


In hematological values we saw mild shifts towards higher cell counts for erythrocytes and
even more subtle for leukocytes and platelets. Additionally, we saw slightly increased MCV, hemoglobin and
hematokrit and a simultaneous decrease in red cell distribution width (RDW) and a trend to
decreased MCHC values. Changes could indicate mild hemoconcentration and effects on osmotic balance.

Insulin:
Increased levels in mutant males (four of five animals above quantification limit of the test).





Immunology

Summary:

We did not observe any genotype-specific alterations.




Cardiovascular

Summary:

Number of specimen analyzed did not allow phenotypic characterization of cardiac electrophysiology.

By echocardiography,
a reduced heart rate and cardiac output and an increased respiration rate was obtained in
mutants. In addition, a reduced interventricular septum width was obtained in male mutants.

Obtained
alterations could be secondary effects caused by differences in body weight.




Pathology

Summary:

LacZ expression is observed in many different tissues. Severe testis atrophy, Leydig- cell hyperplasia and
presence of an X-zone in in male Wsb2 mutants.

 




Bodyweight
Pla2g10 / HEPD0539_1_A05-tm1bPla2g10Targeted mutationHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pubs born 8 14 13 35
Male pubs born 5 9 4 18
Female pubs born 4 5 8 17
M: Fertile
F: Fertile
Fertility:
Male gross findings: Fertile"
Female gross findings: Fertile

Primary Male screen Female screen
Total matings 2 2
Total pups born 9 19
Total litters 3 19
Bone & Cartilage

Summary:

In the primary screening no genotype-specific differences were found between mutants and controls




Behaviour

Summary:

There were no major genotype effects on either open field and prepulse inhibition responding.




Neurology

Summary:

Mutants showed no differences at SHIRPA, grip strength, rotarod performance or ABR compared to mutants.





Eye & Vision

Summary:

We did not find ocular irregularities.




Energy Metabolism

Summary:

No genotype related differences could be detected on energy metabolism.




Clinical Chemistry

Summary:

IpGTT: Slightly increased basal fasting glucose level in female mutants.

Clinical chemistry: Slightly increased
glucose levels in mutants of both sexes and slightly elevated ALP activity in male mutants.
Additionally two outliers in male mutant group: one with high bilirubin level and one with
very high Lipase activity in plasma.

Hematology: RBC, WBC, HCT (both sexes) and PLT
(only females) slightly increased. Trend towards higher MCV and decreased MCHC mainly in females. Possible
hint towards osmotic effects on blood cells.

Insulin: No clear evidence of genotype-related effects,
but mild trend towards increased values in mutant males compared to controls (3 male mutants
above quantification limit)




Immunology

Summary:

We did not observe any genotype-specific alterations.




Cardiovascular

Summary:

By echocardiography, no alterations were found in mutant mice.

By electrocardiography, reduced HRV, and
increased PQ and PR interval durations were found in mutants compared to control mice. However,
number of specimen analyzed by recording ECGs did not allow precise phenotypic characterization.

Thus,
the obtained alterations found by recording ECGs are of unclear relevance.




Pathology

Summary:

No genotype associated Lacz expression was detected. Histological examination using light microscopy did not reveal
any pathological changes that could be attributed to the genotype of the mice.

No
genotype effects in heart weight or body weight




Bodyweight
Fam216a / HEPD0675_7_F06-tm1bFam216aTargeted mutationHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pubs born 11 16 12 39
Male pubs born 3 6 6 15
Female pubs born 8 10 6 24

Fertility:
Male gross findings: "
Female gross findings:

Primary Male screen Female screen
Total matings
Total pups born
Total litters
Bone & Cartilage

Summary:

In the analysis for dysmorphology, bone and cartilage, we did not detect any alterations.




Behaviour

Summary:

There were no major genotype effects on open field behaviour. There was a subtle increased
acoustic reaction at the in a prepulse alone trial.




Neurology

Summary:

Mutants show slightly more tail elevation. No difference for grip strength.




Eye & Vision

Summary:

No eye phenotype for the Fam216a mutants.




Energy Metabolism

Summary:

No obvious differences but too few mutant mice.




Clinical Chemistry

Summary:

IpGTT: Slightly increased weight loss in mutant males and trend towards higher basal fasting glucose
levels in mutants.

Insulin: Only 4 female and 5 male mutants tested. High variance
in female mutants. No clearly genotype-related effects observed

Clinical chemistry: Trends towards lower plasma
phosphate and higher ALP activity in mutants

Hematology: Clearly increased platelet counts in mutants
associated with a trend towards higher platelet volumes in females. but only subtle genotype-related trends
in red blood cell and leukocyte counts.




Cardiovascular

Summary:

By echocardiogarphy, mild alterations without main influence on cardiovascular system were found namely: Reduced wall
width and LVmass mainly in males; Increased FS, EF and HR in males.

By
recording ECGs increased PQ and PR interval duration were found in female mutants compared to
controls. The alterations found are of unclear relevance.

No clear phenotype could be found.





Pathology

Summary:

Body weight ist statistically significant reduced in female mutant mice (p=0,043).

No statistically significant
differences in total and normalized heart weight between mutant and control mice.

Histological examination
using light microscopy did not reveal any pathological changes that could be attributed to the
genotype of the mice.




Bodyweight
Oplah / EPD0244_4_F09-tm1bOplahTargeted mutation

Fertility:
Male gross findings: "
Female gross findings:

Primary Male screen Female screen
Total matings
Total pups born
Total litters
Bone & Cartilage

Summary:

In the analysis for dysmorphology, bone and cartilage, we did not detect any alterations.




Behaviour

Summary:

There were no major genotype effects on open field behaviour and a subtle increase in
prepulse inhibition in the female mutant mice with the opposite effect in the males.




Neurology

Summary:

Subtly reduced grip strength.




Eye & Vision

Summary:

No eye phenotype.




Energy Metabolism

Summary:

Rearing and distance travelled reduced. No clear effects on energy turnover.




Clinical Chemistry

Summary:

IpGTT: AUC 0-30 values slightly increased in mutant females compared to corresponding controls.

Insulin:
Males 4 of 7 high value, females 2 of 8 slightly increased >> unclear relevance.


Clinical chemistry: Slightly decreased values of TIBC and UIBC, increase in calculated transerrin sauration
and HDL-cholesterol, and - in males only - elevated albumin; subtle differences of unclear relevance.


Hematology: No evidence of clearly genotype-dependent effects.




Cardiovascular

Summary:

No alterations found by electrocardiography.

By echocardiography, subtle changes with unclear relevance for the
cardiovascular system were found in females, namely:

Increaesed LVIDd, BW, LVmass,SV and AoDiam, and 
reduced HR and RR.

 




Pathology

Summary:

LacZ positive staining was observed in intestinal wall, ventricle ependymal lining, testis, seminal vesicles, preputial
gland, lung, forestomach, salivary glands, kidney and thymus.

LacZ staining in homozygous mouse is
poorly specific. Expression was observed within ventricular ependymal lining, kidney, and thymus.

Female mutant
mice showed statistically significant increased body weight and tibia length (body size).

Histological analysis
using light microscopy did not reveal any pathological alterations that could be attributed to the
genotype of the mice.




Bodyweight
Hsf2bp / Hsf2bptm1bHsf2bpTargeted mutationHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pubs born 10 31 11 52
Male pubs born 6 24 7 37
Female pubs born 4 7 4 15

Fertility:
Male gross findings: "
Female gross findings:

Primary Male screen Female screen
Total matings
Total pups born
Total litters
Bone & Cartilage

Summary:

In the primary screening no genotype-specific differences were found between mutants and controls.




Behaviour

Summary:

There was a subtle decrease in prepulse inhibition by the mutant mice.




Neurology

Summary:

We observed slightly elevated forepaw grip strength and no difference at SHIRPA, rotarod or ABR.





Eye & Vision

Summary:

We did not find ocular irregularities.




Energy Metabolism

Summary:

We observed hypophagia and a reduced resting metabolic rate. The metabolic fuel utilization trended to
be shifted to lipids.




Clinical Chemistry

Summary:

IpGTT results do not indicate clearly genotype-related differences.

Clinical chemistry of plasma samples collected
from ad libitum fed mice show a mild increase of cholesterol and triglycerides in mutants
compared to controls and a trend towards lower phosphate levels in mutants.

Hematological data
do not provide evidence of genotype-related effects.

Insulin: No evidence of genotype-related effects.




Immunology

Summary:

We did not observe any genotype-specific alterations.




Cardiovascular

Summary:

By echocardiography, increased left ventricular mass and stroke volume was obtained in male mutants. Further,
an increased cardiac output was found mainly in male mutants.

Obtained alterations could be
secondary effects caused by differences in body weight.

Number of male specimen analyzed did
not allow phenotypic characterization of cardiac electrophysiology. Female mutants showed increased R amplitude.




Pathology

Summary:

Male mutant mice show marked testicular atrophy with multifocal vacuolation of Sertoli cells and disruption
of spermatogenesis  (FIgure 166m_13_1637_testis_10x). The lumen of the epididymal duct contains cell debris in
absence of mature spermatozoa.

No genotype associated lacZ expression was detected.



Discussion:

Male mutant mice show marked testicular atrophy with multifocal vacuolation of Sertoli cells and disruption
of spermatogenesis. The lumen of the epididymal duct contains cell debris in absence of mature
spermatozoa. These findings indicate a functional role of HSF2BP in spermatogenesis.

A testis-specific expression
of HSF2BP was reported by Yoshima et al. (1998).

Bodyweight
Myoz1 / HEPD0534_5_A02-tm1bMyoz1Targeted mutationHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pubs born 23 35 23 81
Male pubs born 10 16 9 35
Female pubs born 13 19 14 46
M: Fertile
F: Fertile
Fertility:
Male gross findings: Fertile"
Female gross findings: Fertile

Primary Male screen Female screen
Total matings 2 2
Total pups born 14 14
Total litters 2 2
Bone & Cartilage

Summary:

In the primary screening no genotype-specific differences were found between mutants and controls.




Behaviour

Summary:

The mutant mice were rearing less in the open field and showed decreased locomotor activity
during the second half of the test with decreased locomotor speed. There was also an
increased prepulse inhibition in the mutant mice.




Neurology

Summary:

Mutants showed hypoactivity, reduced grip strength and decreased rotarod latencies. ABR was not different.




Eye & Vision

Summary:

We did not find ocular irregularities.




Energy Metabolism

Summary:

Mutant mice were hypometabolic. Mean and minimum oxygen consumption were decreased when adjusted for body
mass. Only slight hypoactivity could be detected.




Clinical Chemistry

Summary:

We found small, often sex-specific differences between genotypes representing findings of unclear relevance.

IpGTT:
Basel glucose levels show sex-specific genotype-related effects: A significant increase in males and the opposite
trend in females. But no differences in body mass loss or AUC values were observed.


Clinical Chemistry: Almost exclusively sex-specific effects. Lipase activity was mildly increased in mutants of
both sexes. Only in females: Alb, TP increased, Crea decreased; only in males CHO and
HDL increased, Na, urea decreased.

Hematology: Trend towards higher MCV and lower MCHC in
mutants.




Immunology

Summary:

The immunology tests were not performed.




Cardiovascular

Summary:

By echocardiography, a increased left ventricular posterior wall width was observed in female mutants, incraesed 
diastolic left ventriuclar dimension, heart rate, left ventricular volume and stroke volume was observed mainly
in male mutants.

The findings are quite small and subtle and thus of unclear
relevance for the cardiovascular system.




Pathology

Summary:

LacZ Expression was observed in the kidney (vessels in outer medulla (vasa recta)).

Mutant
animals presented a moderate increase in microgranuloma and inflammatory cells in the liver. Female mutant
animals presented in addition inflammatory infiltrates in the salivary glands.

Increased heart weight/body weight
ratio in mutant mice.




Bodyweight
Syk / HEPD0722_4_A07-tm1bSykTargeted mutationHomozygous - Lethal
Viability:
Homozygous - Lethal

Wildtype Heterozygote Homozygote Total
Male and female pubs born 7 21 0 28
Male pubs born 4 10 0 14
Female pubs born 3 11 0 14

Fertility:
Male gross findings: "
Female gross findings:

Primary Male screen Female screen
Total matings
Total pups born
Total litters
Bone & Cartilage

Summary:

Mutant mice showed increased weight, total (DEXA) weight, lean mass, fat mass as well as
bone area, bone mineral content. Bone mineral density was not changed, while volumetric bone mineral
density was decreased. Bone parameters were similarly altered in the lumbar spine.




Behaviour

Summary:

There was decreased distance travelled in the centre of the open field in the mutant
mice as well as decreased centre time by the male mutant mice. No clear genotype
effects on prepulse inhibition were detected.




Energy Metabolism

Summary:

Mutant mice show increased body weight but decreased food uptake. Minimal, average and maximal oxygen
uptake is lower than expected in respect to the body weight of mutant mice. Travelled
distance is reduced in mutants.




Clinical Chemistry

Summary:

IpGTT: Increased body mass and reduced body mass loss by fasting, but no effect on
glucose T0 or AUC values.

Insulin (ad lib.): No evidence of genotype-related differences.


Clinical chemistry: Lowered creatinine and inorg. phosphate in males and elevated ALP in females, are
findings of unclear relevance.

Hematology: No evidence of genotype-related effects.




Immunology

Summary:

There were no defect in immune cell development of het mutant mice .




Cardiovascular

Summary:

ECG and ECHO were performed and only minor changes  without clinically relevance for the cardiovascular
system were found, namely:

Increased heart function, heart rate and aortic diameter in females.


No clear phenotype was found.




Pathology

Summary:

Body weight is significantly increased in male and female mutant mice compared to control mice.


Absolute and normalized (to tibia length) heart weight is increased in mutant compared to
control mice.

Waiting histological analysis.




Bodyweight
Dpp9 / Dpp9-tm1bDpp9Targeted mutationHomozygous - Lethal
Viability:
Homozygous - Lethal

Wildtype Heterozygote Homozygote Total
Male and female pubs born 21 32 0 53
Male pubs born 14 15 0 29
Female pubs born 7 17 0 24

Fertility:
Male gross findings: "
Female gross findings:

Primary Male screen Female screen
Total matings
Total pups born
Total litters
Bone & Cartilage

Summary:

In the primary screening no genotype-specific differences were found between mutants and controls.




Behaviour

Summary:

The mutant mice showed decreased distance travelled in the centre of the open field and
increased prepulse inhibition.




Neurology

Summary:

We observed no differences at SHIRPA, grip strength, rotarod (only 3 mutants per sex analyzed)
and ABR.




Eye & Vision

Summary:

We did not find ocular irregularities.




Energy Metabolism

Summary:

No metabolic phenotype could be detected.




Clinical Chemistry

Summary:

Our results hint towards effects on water/electrolyte and osmotic balance as well as energy (glucose
and fat) metabolism. Renal and/or liver functions seem to be affected.

IpGTT: We found
an increased body mass loss due to food withdrawal in both sexes, increased glucose T0
and AUC 0-30 in males and a trend towards higher AUC 0-30 values also in
females.

Clinical chemistry: Alb, Fe, (ALP, Na, Cl, TP) were increased in both sexes.
Bil and Lip were decreased only in females, Pi in both sexes and CHO, TGL,
(HDL) were decreased only in males.

Hematology: Mainly in males we found Increased WBC,
only in females we observed increased MPV and PDW and increased P-LCR was found in both
sexes. A trend towards decreased RDW was found in both sexes.




Immunology

Summary:

Analysis of splenocytes revealed slightly increased frequencies of CD44 and Ly6C expressing cells within the
CD8+CD4- T cell compartment. 




Cardiovascular

Summary:

Only mild genotype-related differences without relevance for the cardiovascular system were found: reduced diastolic left
ventricular posterior wall width in male mutants.




Pathology

Summary:

LacZ expression was observed in brain (meninges, superficial glial cells (astroglia); cerebellum: bergman glial cells);
lung/aorta (vessel endothelia); kidney (vessels); skin (hairfollicles); acessory glands (vesicular gland) and pancreas (exocrine pancreas).


Histological examination using light microscopy did not reveal any pathological changes that could be
attributed to the genotype of the mice.




Bodyweight
Exph5 / EPD0329_1_G11-tm1bExph5Targeted mutationHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pubs born 23 31 13 67
Male pubs born 10 17 8 35
Female pubs born 13 14 5 32

Behaviour

Summary:

There was a subtle increase in centre distance travelled in the open field and no
clear difference in prepulse inhibition of the acoustic startle response.




Neurology

Summary:

No differences at SHIRPA, grip strength or ABR.




Eye & Vision

Summary:

No eye phenotype.




Energy Metabolism

Summary:

Male mice show reduced body weight.




Clinical Chemistry

Summary:

IpGTT: Lower weight loss by fasting in females, and slightly higher AUC values in both
sexes.

Insulin: Elevated insulin levels mainly in females.

Clinical chemistry: In both sexes
elevated cholesterol and triglyceride levels. In males decreased calcium. In females decreased K, Pi, iron,
transf. sat. and increased TP, albumin, TIBC, UIBC HDL-Cho na glucose.

Hematology: Slightly elevated
WBC, PLT, PCT, MCH, MCHC and RDW in females, elevated HGB, HCT in both sexes
and elevated MCV in males.




Immunology

Summary:

There was no evidence for immunological phenotype. All analyzed leukocyte populations were comparable between mutants
and controls.




Cardiovascular

Summary:

Electrocardiography:

At similar heart rate, QT interval lengths and QT post normalization were decreased
in female mutant mice compared to controls.

Echocardiography:

The echocardiogram parameters were similar
except for the aortic diameter which was observed to be slightly reduced in male mutants
compared to controls.

Despite these observations, the Exph5 cohort did not show any cardiovascular
abnormalities.




Pathology

Summary:

Male mice had decreased heart weight (absolute and normalised by tibia length) compared to control
mice.

Waiting histological analysis.




Bodyweight
Slc22a4 / Slc22a4tm1.1(KOMP)VlcgSlc22a4Targeted mutationHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pubs born 28 39 21 88
Male pubs born 13 18 11 42
Female pubs born 15 21 10 46

Behaviour

Summary:

There was no clear genotype effect on open field behavior or prepulse inhibition of the
acoustic startle response.




Neurology

Summary:

Slightly less urination, no difference at other SHIRPA parameters, ABR or grip strength.




Eye & Vision

Summary:

No eye phenoytpe.




Energy Metabolism

Summary:

Mutant mice show reduced travelled distance and rearing behavior.




Clinical Chemistry

Summary:

IpGTT: No evidence of genotype-related differences.

Insulin (ad lib.): No evidence of genotype-related differences.





Immunology

Summary:

There were no significant differences in the immune cell composition of the spleen between mutants
and controls.




Cardiovascular

Summary:

By echocardiography a reduced aortic diameter was found at the male mutant mice.
This
alterations of heart dimension is mild and therefore not pathologic.No clinically
relevant phenotype could
be found.




Pathology

Summary:

There were no significant differences in body and heart weights between mutant and control mice
at 17 weeks of age.

Waiting histological analyses




Bodyweight
Ostf1 / HEPD0774_7_B06-tm1bOstf1Targeted mutationHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pubs born 25 43 15 83
Male pubs born 11 18 7 36
Female pubs born 14 25 8 47

Fertility:
Male gross findings: "
Female gross findings:

Primary Male screen Female screen
Total matings
Total pups born
Total litters
Bone & Cartilage

Summary:

No morphological or radiological abnormalities were observed.




Behaviour

Summary:

There was increased acoustic startle by the mutant mice. No clear genotype effects on open
field behavior were detected.




Energy Metabolism

Summary:

Mutant mice show reduced minimal, average and maximal oxygen consumption. Furthermore a trend towards a
higher respiratory exchange ratio was observed.




Clinical Chemistry

Summary:

IpGTT: Slightly increased AUC values in male mutants represent a finding of unclear relevance.


Insulin (ad lib.): No clear evidence of genotype-related differences.

Clinical chemistry: Subtle, mostly sex-specific
alterations of enzyme activities (ALAT, ASAT, ALP) and iron metabolism related parameters are findings of
unclear relevance.

Hematology: Subtle genotype-related differences in WBC, PLT and PDW represent findings of
unclear relevance.




Immunology

Summary:

In general, the mutant mice have no major difference on immune cell development in comparison
to the wild type mice.

A slight tendency of higher granulocyte frequency in male
mutant, but it would not be related to the disease outcome.




Cardiovascular

Summary:

ECG and ECHO were performed and subtle changes  with unknown clinical relevance for the cardiovascular
system were found, namely:

Reduced diastolic posterior wall width in males, reduced systolic inner
diameter, increased heart function, reduced left ventricular mass, reduced stroke volume in females, increased heart
rate in males.

The relevance of these findings are unclear.




Pathology

Summary:

There were no differences in body and heart weights between mutant and control mice.


Waiting histological analysis




Bodyweight
Emc3 / EPD0541_2_C06-tm1bEmc3Targeted mutationHomozygous - Lethal
Viability:
Homozygous - Lethal

Wildtype Heterozygote Homozygote Total
Male and female pubs born 10 25 0 35
Male pubs born 4 14 0 18
Female pubs born 6 11 0 17

Fertility:
Male gross findings: "
Female gross findings:

Primary Male screen Female screen
Total matings
Total pups born
Total litters
Bone & Cartilage

Summary:

Compared to wild type mice, mutant animals show increased fat mass.




Behaviour

Summary:

There was increased acoustic startle and a subtle decrease in rearing activity in the open
field.




Neurology

Summary:

Mutants showed a trend towards increased grip strength but reduced rotarod latencies. No difference at
SHIRPA or ABR.




Eye & Vision

Summary:

Increased retinal thickness in the male mutants only. With scheimpflug camera a mild lens opacification
was detected.




Energy Metabolism

Summary:

Mutant mice show trends towards increased body mass and reduced travelled distance.




Clinical Chemistry

Summary:

IpGTT: Genotype-related effects observed in males only, namely increased body weight and decreased AUC values
due to lower peak glucose levels.

Insulin (ad. lib:): No evidence of genotype-related differences.


Clinical chemistry: Subtle elevation of alpha-amylase activity in mutants and slightly elevated potassium and
triglyceride levels and lowered lipase activity in females only, are subtle differences of unclear relevance.


Hematology: No evidence of genotype-related differences.




Immunology

Summary:

No clear immunological deficit was observed.




Cardiovascular

Summary:

By echocardiography  very mild increase in left ventricular posterior wall width in diastole, reduced systolic
left ventricular posterior wall width was found in males. In females the left ventricular mass
was reduced. Thus, mutants hearts show trends towards reduced heart size. The alteratiosn are very
mild and not pathologic.

By recording ECGs increased heart rate in females, reduced atrio-ventricular
conduction time (PR and PQ) in males; increased QRS interval duration and mean SR and
R amplitudes in females were found. Alterations are very mild and have no clinical relevance.


No clear phenotype could be observed.




Pathology

Summary:

Increased body weight in mutant male mice. Abnormal tibia length in mutant female mice. No
effect in heart weight.




Bodyweight
Map3k10 / HEPD0635_8_D03-tm1bMap3k10Targeted mutationHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pubs born 8 14 6 28
Male pubs born 3 7 2 12
Female pubs born 5 7 4 16
M: Fertile
F: Fertile
Fertility:
Male gross findings: Fertile"
Female gross findings: Fertile

Primary Male screen Female screen
Total matings 2 2
Total pups born 11 21
Total litters 3 3
Bone & Cartilage

Summary:

In the primary screening no genotype-specific differences were found between mutants and controls. The number
of male mutants was too small for a statistical analysis of the DXA and X-ray
data.




Behaviour

Summary:

There was increased startle reactivity by the mutant mice and no major genotype effects in
the Open Field.




Neurology

Summary:

Mutants showed increased locomotor activity and more tail elevation at SHIRPA. No differences were detected
for grip strength and rotarod performance.




Eye & Vision

Summary:

no pathologic phenotype




Energy Metabolism

Summary:

Hyperphagia, RER trended to be increased.




Clinical Chemistry

Summary:

Clinical chemistry: More prominent genotype-related differences in males than in females, but most findings observed
in both sexes: Significant increase in plasma cholesterol, HDL-cholesterol, fructosamine, creatinine, calcium and phosphate levels
in mutants. Trends towards higher K, TP, albumin and TIBC values as well as ASAT
and alpha-amylase activities, but lower triglyceride, iron and transferrin saturation in mutants.

Hematology: Trend
towards lower RDW values in mutants compared to controls. Very small difference. Finding of unclear
relevance.

IpGTT: No statistically significant genotype-related effects. In males a trend towards higher fasting
glucose level and AUC 0-30 values in mutants was visible, while most of the female
mutants lost less body mass than corresponding controls due to overnight food withdrawal.

Insulin:
No evidence of genotype-related effects.




Cardiovascular

Summary:

Only mild genotype-related differences without relevance for the cardiovascular system were found:

by echocardiography,
reduced IVSd, LVPWs, and Increased RR.

by electrocardiography, increased HRV.




Pathology

Summary:

LacZ staining observed in brown adipose tissue and in the auricles of the heart.


No statistically significant differences of absolute and to tibia normalized  heart weight were detected comparing
mutant and control mice.

The Map3K10 mutant  mice showed no pathological alterations that could
be associated to the genotype.




Bodyweight
Btbd9 / EPD0631_3_A09-tm1bBtbd9Targeted mutationHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pubs born 8 20 7 35
Male pubs born 2 10 4 16
Female pubs born 6 10 3 19

Fertility:
Male gross findings: "
Female gross findings:

Primary Male screen Female screen
Total matings
Total pups born
Total litters
Bone & Cartilage

Summary:

No morphology abnormalities observed. In X-ray analysis, the number of cervical vertebrae was reduced in
the mutants.




Behaviour

Summary:

There were no clear genotype effects on prepulse inhibition of the acoustic startle response or
on open field behaviour.




Neurology

Summary:

No differences at SHIRPA and Rotarod; grip strength of females was reduced but confounded by
body mass difference. ABR analysis revealed increased sound pressure thresholds for clicks and higher frequencies.





Eye & Vision

Summary:

The Btbd9 mutants showed normal eye morphology, no affected lens transparency and no significant retinal
thickness, but had showed to have reduced number of the main blood vessels.



Discussion:

The Btbd9 mutants have reduced number of the main blood vessels. The retina thickness seems
to not be affected by the mutation. The anterior segment of the eye was not
affected by the mutation, and in general the eye morphology showed normal developed eyes for
the Btbd9 mutants compared to their littermate controls.

Loss of Btbd9 function in mice
was shown to recapitulate several aspects of the human RLS (restless legs syndrome) phenotype, especially
with regard to sleep architecture.

A direct link of Btbd9 function to the possible
effects on the retina is not known, despite knowledge on the expression of the molecule
in the retinal layers: outer and inner nuclear layer.

Energy Metabolism

Summary:

Reduced body mass, reduced rearing.




Clinical Chemistry

Summary:

IpGTT: Decreased body weight in mutants. Increased body mass loss and basal glucose levels in
males.

Clinical chemistry: ALP significantly, CHO (total and HDL) increased in mutants. Only in
males decreased Na and TGL, increased K and ALAT.

Hematology: MPV increased due to
increased proportion of large platelets (PDW and P-LCR increased), mild decrease of MCV, MCH


Insulin: No evidence of genotype-related effects.

 




Cardiovascular

Summary:

By electrocardiogarphy, altered (reduced) PQ and PR interval duration was found in males without relevance
in cardiac function. In females mild increase in QTc dis and reduced SR and R
amplitudes were found. Relevance in cardiac function is unclear.

By echocardiography, reduced IVSd width,
FS, EF and AoDi was found in females with unknown relevance.

Alterations might be
a result of reduced body weight in mutants compared to controls.

 




Pathology

Summary:

LacZ expression was observed within renal papilla of male and female mice.

Statistically significant
decrease of body weight and tibia length in mutant mice. Statistically significant increase of heart
weight normalized to body weight in mutants.

Histological examination using light microscopy did not
reveal any pathological changes that could be attributed to the genome of the mice.



Discussion:

Histological examination using light microscopy did not reveal any pathological changes that could be attributed
to the genome of the mice.

Bodyweight
Msh5 / EPD0638_1_B02-tm1bMsh5Targeted mutationHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pubs born 13 23 14 50
Male pubs born 4 10 7 21
Female pubs born 9 13 7 29

Fertility:
Male gross findings: "
Female gross findings:

Primary Male screen Female screen
Total matings
Total pups born
Total litters
Bone & Cartilage

Summary:

In mutant mice bone mineral density and volumetric bone mineral density were both reduced. Correspondingly,
these measures were also reduced in the lumbar spine. The observed reductions were more pronounced
in female mutant mice.




Behaviour

Summary:

There was increased acoustic startle reactivity by the mutant mice as well as a subtle
decrease in prepulse inhibition by the female mutant mice. No clear differences in open field
behavior were detected.




Neurology

Summary:

Subtle reduction of ABR threshold for 30 kHz. No difference at SHIRPA, grip strength or
rotarod performance.




Energy Metabolism

Summary:

Higher food intake in male mutant mice, reduced rearing behavior in both sexes.




Clinical Chemistry

Summary:

IpGTT: Sexual dimorphism: Increased weight loss by fasting, high variability of glucose T0 levels, improved
glucose tolerance in males. Decreased weight loss by fasting and in trend impaired glucose tolerance
in females.

Insulin ad lib.: No evidence of genotype-related effects.

Clinical chemistry: Decreased
urea and triglycerides in males, elevated ASAT activity and lowered iron and transferrin saturation in
both sexes.

Hematology: An elevated white blood cell count and in trend also elevated
platelet numbers in female mutants as the only genotype-related difference observed represent findings of unclear
relevance.




Immunology

Summary:

Mild alterations of unknown relevance were observed in mutant mice: decreased NK cell frequencies, a
subtle shift of the CD4:CD8 ration towards CD4, going along with a rather activated phenotype
of CD4+ T cells (CD44+CD62L-). NKT cells also showed similar signs of activation (CD44+ CD62L-).
Furthermore, B cell frequencies were increased in female mutants.




Cardiovascular

Summary:

By echocardiography and electrocardiography very mild and subtle alterations without influence on cardiac function were
found, namely:

Mild reduction in Aortic diameter, reduced SR and R ampolitudes in females.
Alterations have no clinical relevance.

No phenoytpe was found.




Pathology

Summary:

Abnormal tibia length in mutant mice. No phenotype for HW or BW




Bodyweight
Csnk1g2 / EPD0801_6_F07-tm1bCsnk1g2Targeted mutationHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pubs born 10 18 12 40
Male pubs born 8 9 6 23
Female pubs born 2 9 6 17

Fertility:
Male gross findings: "
Female gross findings:

Primary Male screen Female screen
Total matings
Total pups born
Total litters
Bone & Cartilage

Summary:

No morphological or radiological abnormalities were observed in these mutant mice.




Behaviour

Summary:

There was increased prepulse inhibition by the mutant mice and a subtle increase in locomotor
activity during the first 5 minutes of the open field.




Neurology

Summary:

Increased locomotor activity (SHIRPA). No difference at ABR, rotarod performance and grip strength.




Eye & Vision

Summary:

The homozygous Csnk1g2 mice show a significant decrease in their retinal thickness.




Energy Metabolism

Summary:

Slightly reduced body mass but higher relative fat content. Hypermetabolic, increased rearing.




Clinical Chemistry

Summary:

IpGTT: Trend towardselevated weight loss due to fasting and slightly increased basal fasting glucose level
mainly in females - subtle difference of unclear relevance.

Insulin: No evidence of genotype-related
differences.

Clinical chemistry: Increased K, Pi, Na, iron, creatinine and urea, and decreased UIBC
and TIBC predominantly in females indicate renal dysfunction.

Hematology: Decreased RBC and WBC, increased
MCV and MCH in mutants, likely indicate osmotic effects and possibly additionally influences on hematopoiesis.





Immunology

Summary:

Minor alterations of unknown relevance were observed: granulocytes and monocytes were slightly increased in spleens
from mutant mice.




Cardiovascular

Summary:

Only very mild genotype-related differences without relevance for the cardiovascular system were found:

Reduced
diastolic left ventricular inner diamter in females and increased fractional shortening and ejection frcation, reduced
PQ and PR interval duration in males.

No phenotype was found.




Pathology

Summary:

LacZ expression was observed within brain (grey matter, olfactory bulb, medulla oblongata), pituitary gland, salivary
glands, tongue, esophagus, stomach, colon, caecum, heart, liver, pancreas, thyroid, thymus, laryngeal and tracheal cartilage,
lung, kidney, urinary bladder, testis, vas deferens, calvaria, rib cage, and vessels.

Histological examination
using light microscopy did not reveal any pathological alterations that could be attributed to the
genotype.

Heart weight/body weight ratio is increased in mutant mice. No effects in body
or absolute heart weight.




Bodyweight
Car4 / EPD0227_6_F12-tm1bCar4Targeted mutationHomozygous - Subviable
Viability:
Homozygous - Subviable

Wildtype Heterozygote Homozygote Total
Male and female pubs born 23 45 1 69
Male pubs born 10 24 0 34
Female pubs born 13 21 1 35
M: _PNM-NMSP_
F: Fertile
Fertility:
Male gross findings: _PNM-NMSP_"
Female gross findings: Fertile

Primary Male screen Female screen
Total matings 1
Total pups born 8
Total litters 8
Bone & Cartilage

Summary:

In the DXA analysis, we detected a significantly increased body weight and lean mass in
males compared to controls.




Behaviour

Summary:

There was increased prepulse inhibition in the male mutant mice with the opposite effect in
the females. The open field behaviour was not assessed in these mice.




Neurology

Summary:

Mutants showed reduced grip strength, more pronounced in males as well as increased rotarod latencies
of females. ABR thresholds were decreased for 18 and 24 kHz tones, also more pronounced
in males.




Eye & Vision

Summary:

We did not find ocular irregularities.




Energy Metabolism

Summary:

Mutant mice were hyperphagic and showed a higher RER. Male mutants were hypermetabolic whereas females
were hypometabolic.




Clinical Chemistry

Summary:

IpGTT:  We found slightly increased body mass loss in males.

Clinical Chemistry: Na was
increased (males), K, Cl, Crea, Ca, ALP (trend: Alb, ASAT, ALAT; LIP, Iron, Bili). Pi
was decreased in females, UIBC in males.

Hematology: We found a (subtle) mild increase
in PLT, MPV, PDW, PCT, P-LCR , trends to higher RBC and lower MCV that
could hint to increased thrombopoietic activity or osmotic effects. In total males were more affected.


Changes could hint towards an impact of the mutation on liver and possibly bone
metabolism, but these are only mild effects.




Immunology

Summary:

We did not observe any genotype-specific alterations.




Cardiovascular

Summary:

By electrocardiography, increased SR and R amplitudes were found in female mutants.

By echocardiography,
increased wall widths mainly in male mutants were found.

All these mostly quite small
differences are findings of unclear relevance.




Pathology

Summary:

Histological examination using light microscopy did not reveal any pathological changes that could be attributed
to the genotype of the mice. LacZ expression was observed in cortex, cerebellum and basal
ganglia of cerebrum.

The analysis of heart weight did not reveal differences between mutant
and control animals




Bodyweight
Pfkfb3 / EPD0519_2_E03-tm1bPfkfb3Targeted mutation

Fertility:
Male gross findings: "
Female gross findings:

Primary Male screen Female screen
Total matings
Total pups born
Total litters
Bone & Cartilage

Summary:

Compared to wild type controls, mutant mice showed incresed fat mass, bone area, and bone
mineral content. Latter resulted in a decrease in volumetric bone mineral density, while bone mineral
density was not affected.




Behaviour

Summary:

There was increased acoustic startle reactivity. Furthermore, rearing activity was decreased in the male mutant
mice during the first 5 minutes.




Neurology

Summary:

Reduced locomotor activity (SHIRPA) of HETs. Slightly increased grip strength coorelated to increased body weight.
No difference at rotarod performance or ABR.




Energy Metabolism

Summary:

Reduced number of mice analyzed due to technical problems. Mutants show reduced minimal, average and
maximal oxygen consumption despite trend towards higher body weight. Reduced rearing behavior.




Clinical Chemistry

Summary:

IpGTT: Elevated body weight but no clear further effect in females. High variability of phenotypic
outcome in males, with elevated basal glucose levels and impaired glucose tolerance in some of
the mutant males.

Insulin (ad lib.): No evidence of clearly genotype-related differences.

Clinical
chemistry: Slightly increased cholesterol (total and HDL, both sexes), and in females albumin, calcium (trend)
and ALP activity (trend) represent subtle differences of unclear relevance.

Hematology: Slightly lowered MCH,
MCHC and RDW values mainly in female mutants represent subtle differences of unclear relevance.




Immunology

Summary:

Mutant mice have a really subtle decrease of CD4/CD8 ration and the difference would not
have clinical relevance.




Cardiovascular

Summary:

ECG and ECHO were performed and only minor changes without relevance for the cardiovascular system
were found, namely: Reduced septum width in males and increased aortic diameter in females.


No clinically relevant differences of the cardiovascular system were found in this line.




Pathology

Summary:

Body weight is significantly increased in mutant females. No effect on heart weight.




Bodyweight
Entpd1 / EPD0156_1_B01-tm1bEntpd1Targeted mutationHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pubs born 22 44 13 79
Male pubs born 8 18 7 33
Female pubs born 14 26 6 46
M: Fertile
F: Fertile
Fertility:
Male gross findings: Fertile"
Female gross findings: Fertile

Primary Male screen Female screen
Total matings 1 2
Total pups born 4 26
Total litters 1 4
Bone & Cartilage

Summary:

In the primary screening no genotype-specific differences were found between mutants and controls. The number
of mice per group was too small for a statistical evaluation of the morphological observation
of the heterozygous mice.




Behaviour

Summary:

There were no major genotype effects on open field behaviour and lower acoustic responses at
background noise and lower sound pressure levels.




Neurology

Summary:

No data from heterozygous mice available for CSD and grip, RR was not different in
heterozygous and homozygous mice, ABR revealed subtle changes in hearing sensitivity in heterozygous but not
in homozygous mice: lower threshold for lower frequencies, increased thresholds for higher frequencies. In addition,
six plus four homozygous mice were measured against 6+6 controls without showing striking differences at
SHIRPA or grip strength.

 




Eye & Vision

Summary:

No eye phenotype for the Entpd1 mutants, both heterozygous and homozygous mutants did not revealed
significant changes when compared to the control littermates.




Energy Metabolism

Summary:

No major effects could be detected. Maximum oxygen consumption was increased in mutant mice.




Clinical Chemistry

Summary:

Clinical Chemistry: Stronger effects seen in heterozygous mice than in homozygous mutants. In homozygous animals
slightly increased liver enzyme activities (ALAT, ASAT, Amylase) and calcium levels. In heterozygous mutants increased
plasma protein levels (TP, Alb), glucose and Amylase activity as well as decreased potassium and
phosphate levels.

Hematology: We find indications of impaired thrombopoiesis and/or platelet function in both,
heterozygous and homozygous mutant mice: Decreased MPV in asssociated with decreased PDW (less large cells) 
in hets; decreased platelet counts but increased MPV and PDW in homs. Slightly increased WBC
in male mutants.

IpGTT: Homozygous female mutants showed decreased basal fasting glucose levels, and
AUC values were smaller for homozygous mutants of both sexes throughout the test, indicating slightly
improved glucose tolerance in these mice. In heterozygous mutants a decreased basal glucose level and
a trend towards lower AUC values was seen in females only.




Cardiovascular

Summary:

By echocardiography, increased respiration rate, reduced IVSd and LVIDd were found in female mutants.


By electrocardiography, increased QRS interval duration, and reduced ST interval duration were found in male
mutants.

No significant genotype effects were found on the cardiovascular function in this line.





Pathology

Summary:

LacZ staining was observed in blood vessels, trachea, lung (strong staining of bronchi, weaker staining
of alveoli), esophagus, pancreas, uterus, urinary bladder, male accessory sexual glands and salivary glands.


Female mutant mice showed statistically significant increased absolute heart weight. Normalized heart weight (to tibia
lenght and body weight) is unchanged compared to controls.

Histological examination of homozygous and
heterozygous mutant mice using light microscopy did not reveal any pathological changes that could be
attributed to the genotype of the mice.




Bodyweight
Eef2kmt / Eef2kmt-tm1bEef2kmtTargeted mutationHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pubs born 25 37 26 88
Male pubs born 13 21 11 45
Female pubs born 12 16 15 43
M: Fertile
F: Fertile
Fertility:
Male gross findings: Fertile"
Female gross findings: Fertile

Primary Male screen Female screen
Total matings 1
Total pups born 10
Total litters 2
Bone & Cartilage

Summary:

In the primary screening no genotype-specific differences were found between mutants and controls.




Behaviour

Summary:

The mutant mice travelled less distance in the centre of the open field during the
first 5 minutes of the test. There was also an increased prepulse inhibition in the
mutant mice at the lowest prepulse intensity tested.




Neurology

Summary:

No differences at SHIRPA, grip strength and ABR. Females performed subtly better on the rotarod.





Eye & Vision

Summary:

We did not find ocular irregularities.




Energy Metabolism

Summary:

No clear differences were found. Males tended to be hypermetabolic but activity levels were rather
reduced.




Clinical Chemistry

Summary:

IpGTT: We observed a trend to increased weight loss and, mainly in females, higher basal
glucose level and AUC values (low variation in controls).

Clinical Chemistry: Wef observed a
trend towards lower urea levels and less ALAT activity in males.

Hematology: We detected
a trend to lower MPV.

We detected only very subtle differences with no clear
genotype effect.




Immunology

Summary:

We found slightly higher frequency of CD11c+MHCclass II+ cells, and a slightly higher proportion of
CD11b+ expressing cells within this population in Fam86 mutants compared to controls.




Cardiovascular

Summary:

Only mild genotype-related differences  without relevance for the cardiovascular system were found

By electrocardiography,
an increased heart rate and reduced RR interval duration was found in mutant mice compared
to control mice.

By echocardiography, a reduced systolic left ventricular diamter was found in
male mutants compared to control mice.




Pathology

Summary:

LacZ expression was detected in brain and testes. Histological examination using light microscopy did not
reveal any pathological changes that could be attributed to the genotype of the mice.




Bodyweight
Adprm / HEPD0690_8_C04-tm1bAdprmTargeted mutationHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pubs born 27 52 17 96
Male pubs born 20 25 7 52
Female pubs born 7 27 10 44

Bone & Cartilage

Summary:

In comparison to wt control mice, mutant mice showed a reduction of body weight, total
(DEXA) weight, lean and fat mass. Further, both bone area and bone mineral content were
reduced in mutant mice, resulting in comparable BMD between mutant and wt mice. However, corresponding
BMD was increased in mutant mice as compared to control mice.




Behaviour

Summary:

There was increased centre time and distance in the open field and decreased acoustic startle
by the male mutant mice.




Neurology

Summary:

No difference at SHIRPA, grip strength. rotarod performance or ABR.




Energy Metabolism

Summary:

Mutant mice show reduced body weight with a trend towards reduced food intake. Furthermore, average
respiratory exchange ratio is reduced in mutatnt mice.




Clinical Chemistry

Summary:

IpGTT: Decreased body weight in mutants, increased weight loss by fasting in males, opposing effects
on fasting basal glucose levels - low in females, high in males, no effect on
AUC.

Insulin (ad lib.): No evidence of genotype-related differences.

Clinical chemistry: Decreased alpha-amylase
activity in females.

Hematology: Elevated MCH and MCHC values in mutants compared to controls.
Lowered MCV and elevated RDW in males only.




Immunology

Summary:

Mutant mice do not have phenotypic alteration in comparison to the control cohort.




Cardiovascular

Summary:

Mild genotype-related differences  with unknown relevance for the cardiovascular system were found:

Reduced diastolic
septum width, systolic posterior wall width (only in males), reduced inner diameter, increased heart rate,
reduced stroke volume, and only in females increased heart function. By ECG increased heart rate
and shortneing of ST interval duration were found in females.

Mutant hearts are smaller
and the heart rate is increased.

Alterations are not pathologic.




Bodyweight