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Clear genotype related differences
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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
Syde1 / HEPD0665_7_B12-tm1bSyde1Targeted mutationHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pups born 15 20 10 45
Male pups born 6 8 3 17
Female pups born 9 12 7 28

Behaviour

Summary:

There were no genotype effects on open field behavior.




Neurology

Summary:

Slightly less urination in HOMs during SHIRPA. No difference for HETs at SHIRPA and none
for both genotypes at grip strength or ABR.




Eye & Vision

Summary:

The Syde1 heterozygous and homozygous mice do not show evident alteretion in the eye.




Energy Metabolism

Summary:

No differences could be detected.




Clinical Chemistry

Summary:

IpGTT: Results provided no evidence of genotype-related differences between homozygous and wild-type mice. heterozygous animals
in contrast had slightly smaller AUC values than control animals due to lower peak glucose
levels.

Clinical chemistry: Homozygous males presented with slightly elevated TP and TIBC values compared
to controls. However, since measured values were still within the normla range of wild-type mice,
this could be an accidental effect. heterozygous male mutants showed more prominent differences compared to
controls, with elevated TP, albumin, triglycerides glucose, calcium and alpha-amylase activity.

Hematology: In heterozygous
males we see slightly elevarted white blood cell counts. Both, heterozygous and homozygous muants show
slight differences in platelet, with slightly lowered MPV and PDW mainly in female het mice
and elevated PLCR in male hom mice compared to controls.

All differences were rather
subtle.




Immunology

Summary:

No evidence for an immunological phenotype, neither in homozygous nor in heterozygous mutants.




Pathology

Summary:

There were no significant differences in body and heart weights between homozygous mutant and control
mice. For statistical analysis of heterozygous mutants, the animal number is too low.

Waiting
histological analysis




Bodyweight
Dis3 / HEPD0659_5_E08-tm1bDis3Targeted mutationHomozygous - Lethal
Viability:
Homozygous - Lethal

Wildtype Heterozygote Homozygote Total
Male and female pups born 10 18 0 28
Male pups born 8 10 0 18
Female pups 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:

Slightly less defecation and more vocalisation at SHIRPA. No difference at grip strength, rotarod performance
or 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
Pepd / Pepdtm1b(KOMP)WtsiPEPDTargeted mutation

Behaviour

Summary:

There was decreased rearing activity, centre time and centre distance in the open field. Acoustic
startle was increased in these mice and there was a subtle decrease in prepulse inhibition
responding.




Neurology

Summary:

No differences at SHIRPA, grip strength.




Eye & Vision

Summary:

The mutant Pepd mice show altered optical disc morphology. Some of the mutant mice present
retinal layers alterations. No effect on the retinal thickness.




Energy Metabolism

Summary:

Lower body mass and less rearing.




Clinical Chemistry

Summary:

IpGTT: Decreased body mass and slightly increased AUC0-30.

Clinical chemistry: Increased ASAT, TIBC and
UIBC in both sexes. Decreased iron levels in male mutants and slightly lowered creatinine mainly
in females.

Hematology: Slight hypochromia in mutants (lowered MCH) in males associated with microcytosis
in some of the mice. Slightly increased MPV, PDW and P-LCR in females.

Some
of the symptoms correlate (low cholesterol, glucose and amylase, highest ASAT values) with high bilirubin
in some of the male mutants and control, which has been observed before as a
strain specific phenotype also in wildtype mice.




Immunology

Summary:

In spleens from mutant mice, we observed relatively decreased B cell frequencies, together with increased
frequencies of neutrophil granulocytes, monocytes and macrophages. This phenotype was more pronounced in male mutants,
where we also observed higher spleen weights. Taken together, this finding points towards inflammation in
these mice.

Frequencies of pre-B cells were also found to be increased in mutant
mice. The frequencies of CD4+ T cells were slightly higher than in the control group,
and within the CD4+ T cell subset, expression of CD25 was increased, and more cells
showed an activated phenotype.




Cardiovascular

Summary:

Electrocardiography:

Heart rate was decreased in mutant mice compared to controls. Concurrently, RR interval
was extended in mutant mice compared to controls.

Furthermore, QT interval lengths was impaired
in mutant compared to controls.

Echocardiography

There are several observations in the Pepd
cohort, namely:

control mice are heavier than mutants.

increased septum wall thickness (IVSd)
during diastolic contraction in females and all mutants compared to controls.

left ventricular inner
diameter impairement in male mutant mice compared to controls.

fractional shortening and ejection fraction
increased in control mice compared to mutants particularly in males.

respiration rate enhanced in
controls, particularly males, compared to mutants.




Pathology

Summary:

Mutant mice had decreased tibia length compared to control mice, irrespectively of sex. There was
a trend to decreased body weight, significantly in males.

One male mouse displayed fibrotic
changes in the myocardium of the left ventricle. There were no other pathological alterations that
could be attributed to the genotype of the mice.




Bodyweight
Ubac2 / HEPD0599_3_A04Ubac2Targeted mutationHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pups born 11 23 8 42
Male pups born 5 14 4 23
Female pups born 6 9 4 19

Bone & Cartilage

Summary:

no alteration in bone mass




Behaviour

Summary:

There was a subtle decreased rearing activity in the open field and increased acoustic startle
and body weight in the males.




Neurology

Summary:

No genotype effect on SHIRPA, grip strength or ABR.




Eye & Vision

Summary:

No evident eye phenotype.




Energy Metabolism

Summary:

No clear difference could be detected.




Clinical Chemistry

Summary:

IpGTT: No evidence of genotype-related differences

Clinical chemistry: Mildly elevated cholesterol (total and HDL)
in males, slightly elevated UIBC and TIBC in mutants - findings of unclear relevance.


Hematology: No evidence of genotype-related differences.




Cardiovascular

Summary:

Ubac2 mutant mice show alterations in ECG parameters (HR, RR and PR) compared to controls
while ECHO parameters were similar.




Pathology

Summary:

There were no significanc differences in body and heart weights between mutant and control mice.
Male mutant mice trended to be heavier.

Waiting histological analysis




Bodyweight
Golt1b / EPD0289_3_F11Golt1bTargeted mutationHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pups born 1 19 12 32
Male pups born 0 10 6 16
Female pups born 1 9 6 16

Behaviour

Summary:

There was decreased locomotor activity and speed in the open field and no genotype effects
on prepulse inhibition of the acoustic startle response.




Neurology

Summary:

Males show increased grip strength. No differences at SHIRPA parameters or ABR.




Eye & Vision

Summary:

No eye alterations were found in the Golt1b mutant mice.




Energy Metabolism

Summary:

No clear genotype related differences could be detected (only 2 female mutants were analyzed).




Clinical Chemistry

Summary:

IpGTT: No evidence of genotype-related differences.

Clinical chemistry: No evidence of genotype-related differences.


Hematology: No evidence of genotype-related differences.




Immunology

Summary:

No evidence for an immunological phenotype.




Cardiovascular

Summary:

No observations in ECG recodings, however, several echocardiography alterations, particularly in female Golt1b mutants, were
affecting the morphology and functionality of the heart.




Pathology

Summary:

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


Histological analysis using light microscopy did not reveal any alteration that could be associated
to the genotype of mutant mice.




Bodyweight
Dnmt3l / HEPD0801_1_E06-tm1bDnmt3lTargeted mutation

Behaviour

Summary:

There was a subtle increased distance in the female mutant mice and no genotype effects
on prepulse inhibition of the acoustic startle response.




Neurology

Summary:

No genotype effect on SHIRPA parameters, grip strength or at ABR.




Eye & Vision

Summary:

The Dnmt3l homozygous mice do not show any evident ophthalmic alteration.




Energy Metabolism

Summary:

No difference.




Immunology

Summary:

There was no evidence for an immunological phenotype.




Cardiovascular

Summary:

There were no obyservations in the electrocardiography and echocardiography recordings. Dnmt3l mutant and control mice
were similar.



Discussion:

There were no obyservations in the electrocardiography and echocardiography recordings. Dnmt3l mutant and control mice
were similar.

Pathology

Summary:

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


Mutant male mice show severe seminiferous tubule degeneration and azoospermia in the epididymis.


 




Bodyweight
Prox2-em1 / CRISPR/CasProx2Genome editingHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pups born 14 26 15 55
Male pups born 6 13 9 28
Female pups born 8 13 6 27

Behaviour

Summary:

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




Neurology

Summary:

Subtle increase of transfer arousal. No genotype effect on grip strength or ABR.




Eye & Vision

Summary:

No retinal phenoytpe due to deficient Prox2.




Energy Metabolism

Summary:

No difference.




Clinical Chemistry

Summary:

IpGTT: Slightly elevated basal fasting glucose in females compared to controls.

Clinical chemistry: Very
mildly lowered sodium,albumin, calcium, cholesterol (total, HDL) creatinine and UIBC mainly in females as compared
to controls.

Hematology: Mildly elevated RDW and PDW (not significant) values in mutants compared
to controls.

Measured values within range of wild-type mice, therefore observed findings are of
unclear relevance,




Immunology

Summary:

The spleen weights and all major immune cell populations were within the normal range. We
did not observe any evidence for an immunological phenotype.




Cardiovascular

Summary:

There were no observations in electrocardiogram and echocardiogram recordings. Prox2 mutant and control mice were
similar.



Discussion:

There were no observations in electrocardiogram and echocardiogram recordings. Prox2 mutant and control mice were
similar.

Pathology

Summary:

Mutant mice had decreased tibia lengths compared to control mice.

Histological examination using light
microscopy did not reveal any pathological changes that could be attributed to the genotype of
the mice. All mutant mice exhibited subcapsular cell hyperplasia in the adrenal gland which is
considered to be a background finding.




Bodyweight
Fut1 / EPD0817_1_C05Fut1Targeted mutationHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pups born 7 29 14 50
Male pups born 4 18 4 26
Female pups born 3 11 10 24

Behaviour

Summary:

There was increased prepulse inhibition and subtly decreased rearing and locomotor activity in the open
field.




Neurology

Summary:

No differences at SHIRPA paramenters, grip strength or ABR.




Eye & Vision

Summary:

No eye phenotype for the homozygous Fut1 mice.




Energy Metabolism

Summary:

No genotype related differences could be detected.




Clinical Chemistry

Summary:

IpGTT: No evidence of clearly genotype-related differences.

Clinical chemistry: Compared to controls low ALAT
and lipase activity in plasma of mutant animals

Hematology: Only in males slightly higher
RDW (anisocytosis) and lowered WBC in mutants.




Immunology

Summary:

There were no significant differences in main splenocyte populations and spleen weights. However, in male
mutants, we observed marginal increase of unclear relevance in some subpopulations: B1 B cells, CD44+CD62L+
CD8+ T cells, CD25+ CD4+ T cells, and NKT cells.




Cardiovascular

Summary:

Electrocardiography:

No observations, Fut1 mutant and control mice were similar.

Echocardiography:


There were morphological (left ventricular internal diameter and mass) and functional (ejection fraction and fractional
shortening, cardiac output and stroke volume) alterations observed in the Fut1 cohort. Solely, male Fut1
mutants were observed to have alterations compared to male controls while female mice were similar.


These alterations could indicate a left ventricular hypertrophy in male Fut1 mutant mice


 



Discussion:

Fut1 male mutant mice show morphological and functional indications of a left ventricular hyperthrophy.


Due to adaptation of chronically increased afterload (aerobic exercise, strength training, age, high blood pressure,
cardiac disease) heart muscle gets enlarged and loses elasticity and partially fails to pump with
as much force as needed (reduced functionality).

Pathology

Summary:

Mutant male mice had increased absolute and normalized heart weights while mutant females displayed no
differences in organ weights.

Waiting histological analysis




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

Wildtype Heterozygote Homozygote Total
Male and female pups born 16 19 0 35
Male pups born 7 8 0 15
Female pups 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 pups born 17 36 0 53
Male pups born 10 15 0 25
Female pups 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 pups born 19 28 12 59
Male pups born 9 18 8 35
Female pups 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 pups born 8 27 5 40
Male pups born 4 17 3 24
Female pups 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
Il4i1 / EPD0369_7_D03-tm1bIl4i1Targeted mutationHomozygous - Subviable
Viability:
Homozygous - Subviable

Wildtype Heterozygote Homozygote Total
Male and female pups born 17 28 6 51
Male pups born 10 13 1 24
Female pups born 7 15 5 27

Behaviour

Summary:

There was increased percent distance travelled in the centre of the open field and increased
centre resting time. A sutble decrease in acoustic startle was detected in the males.




Neurology

Summary:

Invreased locomotor activity (SHIRPA) of HETs. No difference at grip strength or ABR. The six
HOMs analyzed might also be more active.




Eye & Vision

Summary:

No eye phenotype was observed in the heterozygous and the few (n=6) homozygous Il4i1 mice
examined.




Energy Metabolism

Summary:

Male mutant mice show reduced food uptake and RER.




Clinical Chemistry

Summary:

IpGTT: Small opposing effects on weight loss by fasting in males and females, and no
clear effects on basal fasting glucose levels or AUC values.

Clinical chemistry: Slightly increased
iron and calc. transferrin saturation and lowered UIBC and K in mutants. Values still within
the range of wildtype mice.

Hematology: No evidence of genotype-related differences.




Immunology

Summary:

A subtle reduction of effector CD4 T cell subset on mutant mice in both genders
when compared to the controls from the same day. However, when compared to a larger
control pool, the frequencies of these subsets are still within the 50 percentile and thus
within the normal range.




Cardiovascular

Summary:

By echocardiography a significant increase of the left ventricular internal diameter LVID was detected
at the female mutant mice in comparison to their femal peers. These alterations of heart
dimension, mass and function might impact the physiology of the heart. However further analysis are
needed to confirm this potential heart phenotype.

 

By electrocardiography minor
alterations between the mutant and the control mice were detected.  These alterations are marginal and
are therefore not pathologic.

 



Discussion:

The left ventricular internal diameter LVID of the female mutant mice were increased in comparison
to their peers. Note that the readings of the parameter LVID of the control mice
are in the lower range of the reference range. Further, the results of LVID of
the mutant mice are nearly centered within that reference range.  However, based on the comparison
mutant vs. control a significant alteration of LVID was detected. In summary, additional experiments are
needed to confirm and study the potential influence of this variation on the physiology of
the heart.

Pathology

Summary:

There were no significant differences in body and heart weights between heterozygous mutant and control
mice (not enough hom mice for statistical anlysis).

Waiting histological analysis




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

Wildtype Heterozygote Homozygote Total
Male and female pups born 10 31 11 52
Male pups born 6 24 7 37
Female pups 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
Pla2g10 / HEPD0539_1_A05-tm1bPla2g10Targeted mutationHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pups born 11 19 9 39
Male pups born 7 8 7 22
Female pups born 4 11 2 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
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
Fam216a / HEPD0675_7_F06-tm1bFam216aTargeted mutationHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pups born 11 16 12 39
Male pups born 3 6 6 15
Female pups 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
Myoz1 / HEPD0534_5_A02-tm1bMyoz1Targeted mutationHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pups born 23 35 23 81
Male pups born 10 16 9 35
Female pups 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
Zdhhc5 / HEPD0667_1_B01-tm1e.1Zdhhc5Targeted mutationHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pups born 9 17 9 35
Male pups born 4 10 4 18
Female pups born 5 7 5 17

Behaviour

Summary:

There were no genotype effects on open field behavior and acoustic startle was decreased particularly
in the males.




Neurology

Summary:

Increased ABR thresholds of male mutants. No differences at SHIRPA or grip strength.




Eye & Vision

Summary:

Retinal thickness reduced in the homozygous Zdhhc5 mice. Some of the individuals showed
a varying degree of retinal layers alteration at the RPE and/or PR.




Energy Metabolism

Summary:

Mutant mice were hyperactive (distance travelled) and hyperphagic.




Clinical Chemistry

Summary:

IpGTT: No evidence of genotype-related differences.

Clinical chemistry: Slightly elevated K and creatinine levels.
Lowered CHO, TGL and GLS mainly in female mutants. Lowered albumin in males.

Hematology:
Increased mean platelet volume (MPV) and platelet distribution width (PDW) due to high proportion of
large platelets (P-LCR). Mild erythrocytic macrocytosis with elevated MCV and MCH.




Immunology

Summary:

Male mutans presented with increased spleen weights when compared with the control cohort. However, these
spleen weights were still in the normal range of a larger pool of control animals
measured over time. The cellular composition of the spleens was comparable between mutants and controls.





Cardiovascular

Summary:

There were several observations of interest in the electrocardiogram recordings, while the results derived from
the echocardiography were similar in mutant and controls. These data indicate that Zdhhc5 mutant mice
may have alterations in the electrical conducation of the heart, nevertheless, limited number of mutant
mice (n=5) may have an impact on this data set.




Pathology

Summary:

Mutant mice had increased heart weight normalized to body weight compared to control.

/> Histological analysis revealed two male mutant mice with unilateral hydronephrosis. Although this is not
an unusual finding in male mice, in correlation to the high AP value in the
clinical chemistry screen, we consider this to be genotype specific. One female mutant mouse displayed
multifocal basophilic foci in both kidneys, which can be an early sign of nephropathy. The
livers of all mutant animals had focal two multifocal inflammatory infiltrates (microgranuloma) in the liver,
accompanied by apoptotic hepatocytes.
Both males displayed degenerative changes in the testes with vacuolated
seminiferous tubules and multinucleated giant cells. One male mutant suffered from oligospermia.




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

Wildtype Heterozygote Homozygote Total
Male and female pups born 21 32 0 53
Male pups born 14 15 0 29
Female pups 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
Syk / HEPD0722_4_A07-tm1bSykTargeted mutationHomozygous - Lethal
Viability:
Homozygous - Lethal

Wildtype Heterozygote Homozygote Total
Male and female pups born 7 21 0 28
Male pups born 4 10 0 14
Female pups 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
Exph5 / EPD0329_1_G11-tm1bExph5Targeted mutationHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pups born 23 31 13 67
Male pups born 10 17 8 35
Female pups 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.

Microscopical analysis using light microscopy did not reveal any phenotype that could be
associated to the genotype of the mice.




Bodyweight
Thg1l / EPD0456_2_A07-tm1bThg1lTargeted mutationHomozygous - Lethal
Viability:
Homozygous - Lethal

Wildtype Heterozygote Homozygote Total
Male and female pups born 28 40 0 68
Male pups born 17 13 0 30
Female pups born 11 27 0 38

Behaviour

Summary:

There was increased acoustic startle without differences in open field behavior.




Neurology

Summary:

No differences at SHIRPA, grip strength or ABR.




Eye & Vision

Summary:

No eye phenotype.




Clinical Chemistry

Summary:

IpGTT: Elevated fasting glucose level in females, trend to lower AUC 0-30 values in both
sexes. Subtle effects of unclear relevance.

Clinical chemistry: Slightly decreased TP and albumin in
males associated with non-significant trend towards elevated urea and creatinine are findings of unclear relevance.


Hematology: Slightly elevated proportion of large platelets and non-significat trend towards higher MPV in
mutants: Subtle difference of unclear relevance

Insulin: Not quantifiable for technical reasons, no differences
in signal strength.

 




Immunology

Summary:

We observed increased spleen weight in mutant mice of both sexes, but alo in male
control mice. Furthermore, one male control had an increased proportion of myeloid cells, particularly granulocytes
pointing towards inflammation in this mouse.

The CD4/CD8 ratio of T cells was increased
in mutant mice, even though the expression profile of CD44 and L-Selectin on both CD4+
and CD8+ T cells was comparable between the mutants and the controls.

Some other
subpopulation of splenocytes (e.g. % of T cells, B1 B cells, Tregs and NKT cell
subsets) showed subtle alteration when compared to the small control group analysed on the same
day. However, when compared with a larger pool of control animals, these frequencies were still
within the normal range.




Cardiovascular

Summary:

Electrocardiography:

There were no observation except for increased PR lengths in female controls compared
to mutants at similar heart rate.

Echocardiography:

Beside the fact that male mutant
mice were slightly heavier than controls some minor observations were found, namely:

reduced left
ventricular posterior wall thickness in male controls compared to mutants.

higher respiration rate in
mutants.

decreased aortic diameter in female controls compared to mutants.




Pathology

Summary:

Mutant mice had a trend to increased body weight, significant in male mice. Absolute and
normalized spleen weihgts were increased in the mutant mice.

 

Waiting histological analysis





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

Wildtype Heterozygote Homozygote Total
Male and female pups born 28 39 21 88
Male pups born 13 18 11 42
Female pups 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
Map3k10 / HEPD0635_8_D03-tm1bMap3k10Targeted mutationHomozygous - Viable
Viability:
Homozygous - Viable

Wildtype Heterozygote Homozygote Total
Male and female pups born 8 14 6 28
Male pups born 3 7 2 12
Female pups 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