| Gene: 31 | Name: B3galt2 | Family: Carbohydrate Metabolis... | Subfamily: Brainiac | Accession: NM_020025 | GI: 9910135 |
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Gene
31
Summary
of Phenotypic Analysis
Changes related to genotype:
ES cells derived from the 129/OlaHsd
mouse substrain were used to generate chimeric mice. F1 mice were generated by
breeding with C57BL/6 females. The resultant F1N0 heterozygotes were
backcrossed to C57BL/6 mice to generate F1N1 heterozygotes. F2N1 homozygous
mutant mice were produced by intercrossing F1N1 heterozygous males and females.
Wild-type control mice and homozygous mutant mice were evaluated by the
following examinations or tests:
When
compared to age- and gender-matched wild-type control mice, homozygous mutants
were significantly different from wild-types in the Open Field Test (percent
time in central). Mutants spent significantly more time in the central
region of the open field, indicating decreased anxiety as compared to
wild-types.
Homozygous
mutants were significantly different from wild-types in the Open Field Test
(total distance traveled). Mutants were hyperactive, in that they moved
about and explored the open field more than wild-types.
Homozygous mutants were significantly impaired on the Rotarod test,
falling from the accelerating rotarod at slower speeds than
wild-types. This may indicate a deficit in motor coordination.
Homozygous
mutants spent significantly more time immobile on the Tail Suspension
test, indicating a possible depression-like phenotype.
Homozygous
mutants displayed significantly enhanced startle responses to sound stimuli at
110 db and 120 db. Also, a trend was detectable at 100 db intensity.
Gene 31
Behavior
Changes related to genotype:
Homozygous
mutant and wild-type control mice were evaluated for phenotypic changes by
testing on six behavioral tasks: Open field test, Tail suspension test,
Rotarod test, Hot plate test, Startle/PPI, and Metrazol test.
Mouse
ID numbers are as follows:
10
homozygous mutant males (140240, 147879, 147894, 147925, 138408, 147939,
147918, 147897, 156714, 147935)
10 wild-type control males (147919, 147923, 147936, 147916, 140238, 147877,
156711, 147920, 147895, 138410)
ES
cells derived from the 129/OlaHsd mouse substrain were used to generate
chimeric mice. F1 mice were generated by breeding with C57BL/6 females.
The resultant F1N0 heterozygotes were backcrossed to C57BL/6 mice to generate
F1N1 heterozygotes. F2N1 homozygous mutant mice were produced by
intercrossing F1N1 heterozygous males and females.
Behavior Findings:
When compared to age- and gender-matched wild-type control mice, homozygous
mutants were significantly different from wild-types in the Open Field Test
(percent time in central). Mutants spent significantly more time in the
central region of the open field, indicating decreased anxiety as compared to
wild-types.
Homozygous
mutants were significantly different from wild-types in the Open Field Test
(total distance traveled). Mutants were hyperactive, in that they moved
about and explored the open field more than wild-types.
Homozygous mutants were significantly impaired on the Rotarod test,
falling from the accelerating rotarod at slower speeds than
wild-types. This may indicate a deficit in motor coordination.
Homozygous
mutants spent significantly more time immobile on the Tail Suspension
test, indicating a possible depression-like phenotype.
Homozygous
mutants displayed significantly enhanced startle responses to sound stimuli at
110 db and 120 db. Also, a trend was detectable at 100 db intensity.
There
were no other genotype-related differences noted between homozygous mutant and
wild-type control mice for any other parameters evaluated during behavior
testing.
Gene 31
Fertility
Both homozygous mutant males
and females were fertile. Their progeny
were viable until weaning.
Three homozygous mutant mice of each gender were set up in a fertility mating one on one with each other at seven to ten weeks of age. One mating pair (181013, 181015) had no pups. The number of pups born from three litters was recorded. Three weeks later, the live pups were counted and weaned.
Mouse ID numbers are as follows:
3 homozygous mutant males (156720, 159096, 181013)
3 homozygous mutant females (156716, 159092, 181015)
Gene 31
Expression
Summary
RT-PCR Summary:
RNA transcripts are detectable in all tissues analyzed: brain, cortex,
subcortical region, cerebellum, brainstem, olfactory bulb, spinal cord, eye,
Harderian gland, heart, lung, liver, pancreas, kidney, spleen, thymus, lymph
nodes, bone marrow, skin, gallbladder, urinary bladder, pituitary gland,
adrenal gland, salivary gland, skeletal muscle, tongue, stomach, small
intestine, large intestine, cecum, testis, epididymis, seminal vesicle,
coagulating gland, prostate gland, ovary, uterus and white fat. Strongest
signals are observed in white fat.
LacZ Summary:
LacZ (beta-galactosidase) expression is detectable in brain, spinal cord,
sciatic nerve, eye, Harderian glands, thymus, lymph nodes, aorta, heart, lung,
kidney, urinary bladder, trachea, larynx, esophagus, pituitary gland, adrenal
glands, salivary glands, tongue, skeletal muscle, skin, male and female
reproductive systems. X-Gal signals are present in many blood vessels and
adipocytes.
Expression:
Brain
In wholemount staining strong lacZ expression is detectable throughout the
brain: in olfactory bulb, cortex, inferior colliculus, thalamus, hypothalamus
cerebellum and brainstem. On frozen sections strong lacZ expression is
detectable in the dentate gyrus, hypothalamus, cortex piriform and blood
vessels. Further in cerebrum, X-Gal signals are detectable throughout the
cortex, hippocampus, caudate putamen, fornix, ventricles, thalamus, choroid
plexus and corpus callosum. In cerebellum weak lacZ expression is detectable in
meninges, Purkinje cell layer, molecular and granular layer. Many nuclei
throughout the brainstem express lacZ strongly. Strong expression is detectable
in blood vessel walls.
Spinal cord
Strong lacZ expression is detectable in many nuclei of the gray matter. Many
nuclei of myelinated nerve tracts express lacZ moderately to strongly.
Sciatic Nerve
Many Schwann cells express lacZ at variable levels.
Eyes
Strongest lacZ expression is detectable in the inner nuclear layer of the
retina. In addition faint signals are observable in the ganglion layer and lens
epithelium.
Harderian Glands
Strong lacZ expression is detectable in blood vessel walls.
Thymus
Strong lacZ expression is detectable in adjacent adipose tissue.
Lymph Nodes
LacZ expression is detectable in adipocytes of the perinodal fat.
Aorta
Strong lacZ expression is detectable in adjacent adipose tissue.
Heart
Many cardiomyocytes express lacZ strongly. Smooth muscle cells in blood vessel
walls show X-Gal staining. Strong expression is detectable in adipocytes of
adipose tissue.
Lung
Very strong expression is detectable in epithelial cells of bronchi and primary
bronchioli. Smooth muscle cells surrounding bronchioli and in pulmonary vessels
express lacZ.
Kidney
Strong lacZ expression is detectable in all glomeruli. Adipocytes of the
perinephric fat show strong X-Gal signals. Strong lacZ expression is apparent
in blood vessel walls.
Trachea
LacZ expression is detectable in the mucosal epithelium. In surrounding tissues
X-Gal signals are seen in nerve cells, myocytes and adipocytes.
Larynx
Strong lacZ expression is detectable in the epithelium and submucosal glands.
Myocytes of the surrounding muscle layer express lacZ.
Esophagus
Myocytes surrounding the epithelium express lacZ.
Pituitary Gland
LacZ expression is restricted to pars distalis.
Adrenal Glands
Practically all cells of the medulla express lacZ.
Thyroid Gland
Distinct cells in the thyroid gland express lacZ strongly.
Parathyroid Gland
Scattered, weak lacZ expression is detectable in the parathyroid gland.
Salivary Glands
Strong lacZ expression is detectable in epithelial cells of ducts. Few acinar
cells of the sublingual and submandibular glands express lacZ.
Tongue
LacZ expression is detectable in the epithelium, nerves and muscle layer.
Skeletal Muscle
Strong lacZ expression is detectable in blood vessel walls.
Skin
LacZ expression is detectable in dermis, hair follicles and sebaceous glands.
Skin of the Ear
LacZ expression is detectable in dermis, hair follicles, sebaceous glands and adipose
tissue.
Male Reproductive Systems
Testis
Strong lacZ expression is detectable in few cross-sections of seminiferous
tubules of one male. Analyzing a second male displayed only weak expression in
the seminiferous tubules. This may suggest that lacZ expression is restricted
to specific developmental stages. Another possible explanation is that we are
at or below threshold of detection using the X-Gal assay.
Strong lacZ expression is detectable in blood vessel walls.
Penis
LacZ expression is detectable in os, fibroblasts and nerve cells.
Coagulating Gland
Few epithelial cells display X-Gal staining. Strong lacZ expression is
detectable in blood vessels.
Prostate and Ampullary Gland
Adipocytes, myocytes and few epithelial cells display lacZ expression.
Female Reproductive Systems
Ovary
LacZ expression is detectable in blood vessels.
Oviduct/Uterus
LacZ expression is detectable in blood vessels.
No Expression:
LacZ expression is not detected in spleen, bone marrow, liver, gallbladder,
pancreas and urinary bladder.
Gene 31
Densitometry
There were no significant differences detected in the homozygous mutant mice
when compared with age- and gender-matched wild-type control mice.
The following mice were evaluated by dual-energy x-ray absorptiometry.
49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (138396, 138400, 138413)
3 homozygous mutant males (138394, 138401, 138405)
2 wild-type control females (138398, 138411)
2 wild-type control males (138393, 138395)
300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (138391, 140244)
2 homozygous mutant males (159098, 178218)
2 wild-type control females (138386, 140250)
2 wild-type control males (171277, 183471)
Bone Mineral Density (BMD in g/cm2 ), fat % (fat percent expressed
as a percentage of body soft tissue compartment), and R-value of soft tissue
were calculated from Bone Mineral Content (BMC in g), bone and tissue areas (cm2 ), and total tissue mass
(g) generated by a PIXImus densitometer.
Densitometric Findings:
Compared to contemporary wild-type mice, but not
to historical control populations, a 300 day cohort homozygous mutant male
(178218) has a lower fat %. We are not presenting this as a phenotypic change
but are reporting it for your consideration. Incidental densitometric
differences were present between some mice. These findings were considered to
represent background differences occasionally seen in this strain of mice,
differences due to spontaneous disease, age-related differences, and/or differences
of a nonspecific etiology. They were not considered to be genotype related.
Gene 31
Histopathology
There were no significant differences detected in the homozygous mutant mice
when compared with age- and gender-matched wild-type control mice.
Tissues from the following mice were evaluated histologically.
49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (138396, 138400, 138413)
3 homozygous mutant males (138394, 138401, 138405)
2 wild-type control females (138398, 138411)
2 wild-type control males (138393, 138395)
300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (138391, 140244)
2 homozygous mutant males (159098, 178218)
2 wild-type control females (138386, 140250)
2 wild-type control males (171277, 183471)
No Significant Abnormalities:
Tissues examined and considered to have no genotypically-significant
abnormality: brain, pituitary gland, ears, nasal cavity, salivary glands, oral
cavity, lymph nodes, aorta, lungs, gallbladder, pancreas, spleen, kidneys,
urinary bladder, stomach, small and large intestines, larynx, esophagus,
trachea, thyroid gland, thymus gland, tongue, skeletal muscle, sciatic nerve,
mammary glands, vertebrae, spinal cord, bone (skull, sternum, femur, tibia, and
stifle joint), reproductive tract including gonads, eyes, Harderian glands,
integumentary system (skin and either clitoral or preputial glands), and bone
marrow.
Bone marrow was examined in sections of sternum, vertebrae, and/or femur and
tibia. Marrow cellularity, myeloid:erythroid (M:E) ratio, myeloid and erythroid
maturation sequences, and numbers of megakaryocytes were evaluated.
Incidental lesions were present in some tissues. These findings are considered
to represent background lesions occasionally seen in this strain of mice,
lesions due to spontaneous disease, age-related lesions, and/or lesions of a
nonspecific etiology. They are not considered to be genotype related.
Gene 31
Necropsy
There were no significant differences detected in the homozygous mutant mice
when compared with age- and gender-matched wild-type control mice.
The following mice were necropsied. Body weight, body length, and organ weights
were obtained and gross pathological findings were recorded.
49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (138396, 138400, 138413)
3 homozygous mutant males (138394, 138401, 138405)
2 wild-type control females (138398, 138411)
2 wild-type control males (138393, 138395)
300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (138391, 140244)
2 homozygous mutant males (159098, 178218)
2 wild-type control females (138386, 140250)
2 wild-type control males (171277, 183471)
Mice were examined for the following observables: adrenal glands, body length,
body weight, bone marrow, bone-cranium, bone-femur, bone-sternum, bone-stifle
joint, bone-vertebral column, brain, cecum, colon, duodenum, epididymis-seminal
vesicle, esophagus, eyes, gallbladder, general appearance, Harderian glands,
heart, heart weight, ileum, jejunum, kidneys, kidney weight, liver, liver
weight, lungs, lymph nodes, mesentery, ovaries, pancreas, penis, salivary
glands, sciatic nerve, scrotum, skeletal muscle, skin, skinned mouse, spleen,
spleen weight, stomach, testes, testes-epididymis weight, thymus, thymus
weight, tongue, trachea, urinary bladder, urine, uterus and vagina (gender
specific observables apply to appropriate gender).
Necropsy Findings:
There were no genotype-related or biologically significant differences noted
between mutant and wild-type control mice for any of the parameters evaluated
at necropsy. Incidental lesions were present in some tissues. For example, a
homozygous mutant female (138391) was reported to have a splenic nodule for
which there was no histologic correlate. These findings were considered to
represent background lesions occasionally seen in this strain of mice, lesions
due to spontaneous disease, age-related lesions, and/or lesions of a
nonspecific etiology. They were not considered to be genotype related.
Body and Organ Weight Findings:
Body weights of all 49 day cohort homozygous mutant males were lower than those
of age- and gender-matched wild-type control mice. Spleen, liver, and kidney
weights and/or organ weight to body weight ratios were also slightly lower for
these homozygous mutant males than for wild-type control males. Body
weights of both 300 day cohort homozygous mutant males were lower than a
contemporary wild-type control mouse but not historical population controls. We
are not presenting these findings as phenotypic changes but are reporting
them for your consideration.
Increased spleen weight in a 49 day homozygous mutant female (138400)
correlated with increased extramedullary hematopoiesis, an incidental finding.
Other differences in body length,
body weight, organ weights, and/or organ weight to body weight ratios were
present between individual mice. The variability between mice usually fell
within our historical reference ranges and was not correlated with genotype.
Gene 31
Clinical
Chemistry
There were no significant differences detected in the homozygous mutant mice
when compared with age- and gender-matched wild-type control mice.
Serum samples from the following mice were evaluated by a clinical biochemistry
panel.
49 Day Cohort Mouse ID numbers
are as follows:
3 homozygous mutant females (138396, 138400, 138413)
3 homozygous mutant males (138394, 138401, 138405)
2 wild-type control females (138387, 138411)
2 wild-type control males (138393, 138395)
90 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (138391, 140244, 147911, 175986)
3 homozygous mutant males (173234, 178217, 188907)
4 wild-type control females (138386, 140250, 147931, 166412)
4 wild-type control males (159100, 173231, 183469, 183471)
180 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (138391, 140244, 147911, 147912)
4 homozygous mutant males (159098, 173234, 178218, 188907)
4 wild-type control females (138386, 140250, 147930, 147931)
4 wild-type control males (159100, 173231, 183469, 183471)
300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (138391, 140244)
2 homozygous mutant males (159098, 178218)
2 wild-type control females (138386, 140250)
2 wild-type control males (171277, 183471)
Compared to contemporary wild-type mice, but not to historical population
controls, values for HDL are higher in homozygous mutant females at 49, 90 and
180 days and in homozygous mutant males at 49 and 180 days. We are not
presenting these findings as phenotypic changes but are reporting them for your
consideration. Values for the other various analytes evaluated were generally
similar between homozygous mutant and wild-type control mice. Variations in
clinical chemistry values were not consistent with genotype and thus were not
considered phenotypically relevant.
Gene 31
Hematology
There were no significant differences detected in the homozygous mutant mice
when compared with age- and gender-matched wild-type control mice.
Blood samples from the following mice were evaluated by a complete blood count
and differential cell count.
49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (138396, 138413, 159076)
3 homozygous mutant males (138394, 138401, 178217)
2 wild-type control females (138387, 138398)
2 wild-type control males (138393, 138402)
90 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (138391, 140244, 147911, 147912)
4 homozygous mutant males (159098, 173234, 178218, 188907)
4 wild-type control females (138386, 140250, 147930, 147931)
4 wild-type control males (159100, 173231, 183469, 183471)
180 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (138391, 140244, 147911, 147912)
3 homozygous mutant males (159098, 173234, 178218)
4 wild-type control females (138386, 140250, 147930, 147931)
4 wild-type control males (159100, 173231, 183469, 183471)
300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (138391, 140244)
2 homozygous mutant males (159098, 178218)
2 wild-type control females (138386, 140250)
2 wild-type control males (171277, 183471)
Although minor variations of hematological values were present in some mice,
these changes were not consistent with genotype and thus were not considered
phenotypically relevant.
Gene 31
Physical
Examination
There were no significant differences detected in the homozygous mutant mice
when compared with age- and gender-matched wild-type control mice.
The following mice were evaluated by physical examination.
49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (138396, 138400, 138413)
3 homozygous mutant males (138394, 138401, 138405)
2 wild-type control females (138398, 138411)
2 wild-type control males (138393, 138395)
300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (138391, 140244)
2 homozygous mutant males (159098, 178218)
2 wild-type control females (138386, 140250)
2 wild-type control males (171277, 183471)
Mice were examined for the following observables: anus, behavior, body shape,
claws, coat - fur, coat color - back, coat color - belly, ear - left, ear -
right, eye - left, eye - right, eye color - left, eye color - right, feces,
feces color, feces exam, forelimb - left, forelimb - right, forelimb number of
amputated digits - left, forelimb number of amputated digits - right, forelimb
number of digits - left, forelimb number of digits - right, general appearance,
genitals - female, genitals - male, hair type, head shape, hindlimb - left,
hindlimb - right, hindlimb number of amputated digits - left, hindlimb number
of amputated digits - right, hindlimb number of digits - left, hindlimb number
of digits - right, injuries, lesions, limb shape, locomotor, lumps - masses,
mammary glands exam, mice in cage, respiration, skin appearance, snout,
swelling - joints, tail, teeth color, teeth length, urine, urine color, urine
exam and whiskers (gender specific observables apply to appropriate gender).
Individual homozygous mutant mice had only occasional minor differences in
observed physical features compared to wild-type control mice. These findings
are considered to represent individual variability, background features
occasionally seen in this strain of mice, findings due to spontaneous disease,
age-related findings, and/or findings of a nonspecific etiology. However, none
of these differences was regarded as biologically significant or genotype
related.
Gene 31
Aging Metrics
There
were no significant differences detected in the homozygous mutant mice when
compared with age- and gender-matched wild-type control mice.
Body
weights and body lengths were measured for mice at 49, 90, 180, and 300 days of
age.
49
Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (138391, 140244, 147911, 147912)
4 homozygous mutant males (159098, 173234, 178218, 188907)
4 wild-type control females (138386, 140250, 147930, 147931)
4 wild-type control males (159100, 173231, 183469, 183471)
90 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (138391, 140244, 147911, 147912)
4 homozygous mutant males (159098, 173234, 178218, 188907)
4 wild-type control females (138386, 140250, 147930, 147931)
4 wild-type control males (159100, 173231, 183469, 183471)
180 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (138391, 140244, 147911, 147912)
4 homozygous mutant males (159098, 173234, 178218, 188907)
4 wild-type control females (138386, 140250, 147930, 147931)
4 wild-type control males (159100, 173231, 183469, 183471)
300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (147871, 147912)
3 homozygous mutant males (159098, 178217, 188907)
2 wild-type control females (147930, 147931)
4 wild-type control males (159100, 171281, 183471, 190735)
Body Weight and Length Findings:
Compared
to contemporary wild-type control males, but not compared to historical
population controls, the homozygous males tended to have lower body weights and
body weight to body length ratios at 49, 90, and 180 days, and in one of three
homozygous mutant males (188907) at 300 days. We are not reporting these
findings as phenotypic changes but are presenting them for your consideration.
Other differences in body length and body weight were present between individual mice. The variability between mice usually fell within our historical reference ranges and was not correlated with genotype.