| Gene: 21 | Name: B3gnt1 | Family: Carbohydrate Metabolis... | Subfamily: Brainiac | Accession: AF092050 | GI: 9755418 |
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Gene 21
Summary
of Phenotypic Analysis
Changes
related to genotype:
There
were no other significant differences detected in the homozygous mutant animals
when compared with age- and gender-matched wild-type control mice.
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. F2
homozygous mutant mice were produced by intercrossing F1 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
displayed a significant increase in the amount of time they spent
exploring the central region during open field testing. This may indicate
less fear or decreased anxiety. Also, tail suspension testing revealed a
significant increase in the amount of time homozygous mutants remain immobile,
compared to wild-type littermates. This may be associated with an
increased depression-like state.
Gene 21
Behavior
Changes related to genotype:
Homozygous
mutant and wild-type control mice were evaluated for phenotypic changes by
testing on five behavioral tasks: Open field test, Tail suspension test,
Rotarod test, Hot plate test, Startle/PPI, and Metrazol test.
Mouse
ID numbers are as follows for the N1 generation:
9 homozygous mutant males (154677, 154680, 154689, 154693, 161184, 170125,
170127, 172566, 200732)
12 wild-type control males (154678, 154679, 154688, 154690, 154691, 161193,
161194, 161196, 170126, 172570, 172571, 200735)
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 displayed a significant increase in the amount of time they spent
exploring the central region during open field testing. This may indicate
less fear or decreased anxiety. Also, tail suspension testing revealed a
significant increase in the amount of time homozygous mutants remain immobile,
compared to wild-type littermates. This may be associated with an
increased depression-like state.
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 21
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 thirteen weeks of age. Two of the male and female pairs (178043 and 178047, 178045 and 178048) produced only two litters that were viable at weaning age. For the third pair (224993 and 240253), t he 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 (178043, 178045, 224993)
3 homozygous mutant females (178047, 178048, 240253)
Gene 21
Expression
Summary
RT-PCR Summary:
RNA transcripts are detectable in all tissues analyzed: brain, cortex,
subcortical region, cerebellum, brainstem, olfactory bulb, eye, 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
and uterus.
LacZ Summary:
LacZ (beta-galactosidase) expression is detectable in brain and testis.
Expression:
Brain
In wholemount staining very faint X-Gal signals are detectable ventrally.
Male Reproductive Systems
Testis
Many spermatogenic cells of the seminiferous tubules show X-Gal staining.
No Expression:
LacZ (beta-galactosidase) expression is not detected in: spinal cord, sciatic
nerve, eye, Harderian glands, thymus, spleen, lymph nodes, bone marrow, aorta,
heart, lung, liver, gallbladder, pancreas, kidney, urinary bladder, larynx,
trachea, esophagus, thyroid gland, parathyroid gland, pituitary gland, adrenal
glands, salivary glands, tongue, skeletal muscle, skin, and female reproductive
systems.
Comparing RT-PCR with lacZ data suggests that the lacZ reporter gene does not
fully reflect the endogenous expression pattern.
Gene 21
Densitometry
There
were no significant differences detected in the homozygous mutant animals 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:
2 homozygous mutant females (135395, 135406)
3 homozygous mutant males (135399, 138902, 138903)
2 wild-type control females (135398, 135404)
2 wild-type control males (150179, 150181)
300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (154658, 203889)
2 homozygous mutant males (215346, 225789)
2 wild-type control females (154660, 196619)
2 wild-type control males (196617, 201901)
Bone Mineral Density (BMD in g/cm2 ), fat % (fat percentage expressed as a
percentage of the soft tissue compartment), and R-value of soft tissue were
calculated from Bone Mineral Content (BMC in g), bone and tissue areas (cm2 ), total tissue mass (g) generated by a PIXImus
densitometer.
Densitometric
Findings:
Certain
changes were present in some mice that could occur spontaneously in mice of
this age group. For example, two homozygous mutant female mice
(154658, 203889) at 300 days had decreased body fat %. We have not
reported these findings as phenotypic changes, but we have presented them here
for your consideration. Other incidental densitometric differences may have
been present between some mice. These findings are considered to represent
background differences occasionally seen in this strain of mice, differences
due to spontaneous disease, age-related changes, differences due to procedural
artifacts, and/or differences of a nonspecific etiology. They are not
considered to be genotype related.
Gene 21
Histopathology
There were no significant differences detected in the homozygous mutant animals
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 (135395, 135405, 135406)
3 homozygous mutant males (135399, 138902, 138903)
2 wild-type control females (135398, 135404)
2 wild-type control males (150179, 150181)
300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (154658, 203889)
2 homozygous mutant males (215346, 225789)
2 wild-type control females (154660, 196619)
2 wild-type control males (196617, 201901)
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.
Certain histopathological lesions, including: mild bone marrow hypocellularity
in two homozygous mutant females (135405, 135406) at 49 days; and, mild
multifocal necrosis with mineralization in brown adipose tissue, moderate focal
necrosis with mineralization in fat associated with the pancreas, and mild
thymic atrophy in one homozygous mutant female (135405), were present that
occasionally occur spontaneously in mice of this age group. Also, two
homozygous mutant males (215346, 225789) had minimal to mild retinal dysplasia
at 300 days. We are not reporting these findings as a phenotypic change,
but we present them here for your consideration.
Incidental lesions may have been 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, lesions due to
procedural artifacts and/or lesions of a nonspecific etiology. They are not
considered to be genotype related.
Gene 21
Necropsy
There were no significant differences detected in the homozygous mutant animals
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 (135395, 135405, 135406)
3 homozygous mutant males (135399, 138902, 138903)
2 wild-type control females (135398, 135404)
2 wild-type control males (150179, 150181)
300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (154658, 203889)
2 homozygous mutant males (215346, 225789)
2 wild-type control females (154660, 196619)
2 wild-type control males (196617, 201901)
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 may have been present in some tissues. These
findings were considered to represent background lesions occasionally seen in
this strain of mice, lesions due to spontaneous disease, age-related lesions,
lesions due to procedural artifacts, and/or lesions of a nonspecific etiology.
They were not considered to be genotype related.
Body and Organ Weight Findings:
One homozygous mutant female (135405) at 49 days had low body weight,
reduced body length and low organ weights compared to concurrent control mice
and historical reference ranges. This mouse was noted to be dwarfed at physical
examination. One homozygous mutant male (225789) at 300 days had increased
spleen weight and spleen weight to body weight ratio and this finding was
histologically correlated with mild increased extramedullary hematopoiesis in
the spleen. We are not reporting these findings as phenotypic changes, but we
present them here for your consideration.
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 21
Clinical
Chemistry
There were no significant differences detected in the homozygous mutant animals
when compared with age- and gender-matched wild-type control mice.
Serum samples from the following mice were evaluated by a clinical biochemistry
panel. The data are compiled from the N1F2 and N2F2 generations.
49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (135406, 142328, 179481)
3 homozygous mutant males (135399, 138902, 138903)
2 wild-type control females (135404, 142330)
2 wild-type control males (150179, 150181)
90 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (154658, 154669, 154696, 161190)
3 homozygous mutant males (215346, 225789, 327768)
4 wild-type control females (154660, 154666, 154668, 161189)
4 wild-type control males (196617, 201901, 214503, 215343)
180 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (154658, 154669, 154696, 161190)
2 homozygous mutant males (215346, 225789)
4 wild-type control females (154660, 154666, 154668, 161189)
4 wild-type control males (196617, 201901, 214503, 215343)
300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (154658, 203889)
2 homozygous mutant males (215346, 225789)
2 wild-type control females (154660, 196619)
2 wild-type control males (196617, 201901)
When compared to age- and gender-matched wild-type control mice, two
300-day homozygous mutant females (154658, 203889) and one 300-day homozygous
mutant male (215346) had an increased level of Blood Urea
Nitrogen. Also one 300-day homozygous mutant male (215346) had low
level of Cholesterol, High Density Lipoprotein and Triglycerides .We are not
reporting these findings as phenotypic changes, but we present them here for
your consideration.
Values
for the various analytes evaluated were generally similar between homozygous
mutant and wild-type control mice. Variations in clinical chemistry values, if
present, were not consistent with genotype and thus were not considered
phenotypically relevant.
Gene 21
Hematology
There were no significant differences detected in the homozygous mutant animals
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. The data are compiled from the N1F2 and N2F2
generations.
49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (135405, 138899, 179483)
3 homozygous mutant males (135399, 138902, 138903)
2 wild-type control females (135398, 135404)
2 wild-type control males (150179, 150181)
90 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (154658, 154669, 154696, 161190)
3 homozygous mutant males (215346, 225789, 327768)
4 wild-type control females (154660, 154666, 154668, 161189)
4 wild-type control males (196617, 201901, 210997, 214503)
180 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (154658, 154669, 154696, 161190)
2 homozygous mutant males (215346, 225789)
4 wild-type control females (154660, 154666, 154668, 161189)
4 wild-type control males (196617, 201901, 214503, 215343)
300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (154658, 203889)
1 homozygous mutant male (215346)
2 wild-type control females (154660, 196619)
2 wild-type control males (196617, 201901)
Although minor variations of hematological values were present in some animals,
these changes were not consistent with genotype and thus were not considered
phenotypically relevant.
Gene 21
Physical
Examination
There were no significant differences detected in the homozygous mutant animals
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 (135395, 135405, 135406)
3 homozygous mutant males (135399, 138902, 138903)
2 wild-type control females (135398, 135404)
2 wild-type control males (150179, 150181)
300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (154658, 203889)
2 homozygous mutant males (215346, 225789)
2 wild-type control females (154660, 196619)
2 wild-type control males (196617, 201901)
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).
When compared to age- and gender-matched wild-type control mice one homozygous
female (135405) was weak, dehydrated, and dwarfed, with a hunched body and
abnormal, overgrown teeth. We are not reporting these findings as phenotypic
changes, but we present them here for your consideration.
There were no other genotype-related or biologically significant differences
noted between mutant and wild-type control mice for any of the parameters
evaluated at physical examination.
Gene 21
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 (154658, 154669, 154696, 161190)
5 homozygous mutant males (214501, 214504, 215346, 225789, 310366)
3 wild-type control females (154660, 154668, 161189)
4 wild-type control males (196617, 201901, 210997, 214503)
90 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (154658, 154669, 154696, 161190)
3 homozygous mutant males (215346, 225789, 327768)
3 wild-type control females (154660, 154668, 161189)
4 wild-type control males (196617, 201901, 210997, 214503)
180 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (154658, 154669, 154696, 161190)
4 wild-type control females (154660, 154666, 154668, 161189)
3 wild-type control males (196617, 201901, 214503)
300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (154696, 179477)
2 wild-type control females (201906, 201908)
2 wild-type control males (214503, 215343)
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.