| Gene: 799 | Name: similar to metabotropic glut... | Family: GPCR | Subfamily: Metabotropic Glutamate | Accession: XM_144986 | GI: 28544598 |
|---|
Gene 799
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 Rotarod test. Mutants fell from the accelerating rotarod slower speeds. This may indicate a motor deficit.
Homozygous mutants were significantly different from wild-types in the metrazol test. Mutants required a lower dose of metrazol before displaying tonic extension and death.
Gene 799
Behavior
Changes related to genotype:
Homozygous
mutant and wild-type control mice were evaluated for phenotypic changes by
testing on seven behavioral tasks: Open field test, Tail suspension test,
Rotarod test, Hot plate test, Startle/PPI, Tail flick, and Metrazol test.
Mouse
ID numbers are as follows:
10
homozygous mutant males (136271, 136273, 145079, 147535, 154357, 156832,
156834, 161212, 188713, 188715)
10 wild-type control males (136270, 136272, 145075, 147538, 154359, 156836,
161208, 188682, 188684, 188716)
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 Rotarod test.
Mutants fell from the accelerating rotarod slower speeds. This may indicate
a motor deficit.
Homozygous
mutants were significantly different from wild-types in the metrazol test.
Mutants required a lower dose of metrazol before displaying tonic extension and
death.
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 799
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. The number of pups born from three litters was recorded. All three matings had only one litter born. Three weeks later, the live pups were counted and weaned.
Mouse ID numbers are as follows:
3 homozygous mutant males (159253, 175902, 175903)
3 homozygous mutant females (159256, 175908, 175906)
Gene
799
Expression
Summary
RT-PCR Summary:
RNA transcripts are detectable in brain, cortex, subcortical region,
cerebellum, brainstem, olfactory bulb, spinal cord, eye, heart, kidney,
pituitary gland, adrenal gland, stomach, large intestine, seminal vesicle,
coagulating gland, ovary and uterus.
No RNA transcripts are detectable in Harderian gland, lung, liver, pancreas,
spleen, thymus, lymph nodes, bone marrow, skin, gallbladder, urinary bladder,
salivary gland, skeletal muscle, tongue, small intestine, cecum, testis,
epididymis, prostate gland and white fat.
LacZ Summary:
LacZ (beta-galactosidase) expression is detectable in brain, spinal cord, eye,
spleen, lymph nodes, esophagus, parathyroid gland, pituitary gland, salivary
glands, tongue, male and female reproductive systems.
Expression:
Brain
In wholemount staining strong lacZ expression is detectable in olfactory bulbs,
cortex, thalamus, hypothalamus and cerebellum. Weaker staining is detectable in
brainstem. On coronal sections strong lacZ expression is detectable in cortex,
hippocampus, thalamus. Weaker expression is detectable in caudate putamen,
lateral septal nuclei, inferior colliculus, third ventricle and hypothalamus.
In cerebellum strongest expression is apparent in Purkinje cell. Further, X-Gal
signals are present in white matter, fourth ventricle and brainstem.
Spinal cord
Strong lacZ expression is detectable in nuclei of the dorsal horns. Weaker
signals are present in cells of the central canal
Eyes
Moderate lacZ expression is detectable in epithelial cells of the lens
epithelium. Faint X-Gal signals are present in the inner nuclear and ganglion
cell layer of the retina.
Spleen
LacZ expression is detectable in the capsule.
Lymph Nodes
Strong lacZ expression is detectable in few adipocytes of surrounding adipose
tissue.
Esophagus
Faint to moderate lacZ expression is detectable in the mucosa.
Parathyroid Gland
Very faint lacZ staining is detectable in few cells of the parathyroid gland.
Pituitary Gland
Faint -Gal signals are apparent in pars distalis and pars intermedia.
Salivary Glands
Moderate to strong lacZ expression is detectable in ganglia.
Tongue
Strong lacZ expression is detectable in blood vessels.
Male Reproductive Systems
Testis
Strong lacZ expression is detectable in interstitial cells. Faint signals are
detectable in spermatogenic cells.
Seminal Vesicles
Strong lacZ expression is detectable in myocytes of the capsule.
Coagulating Gland
Moderate to strong lacZ expression is detectable in myocytes of the capsule.
Prostate and Ampullary Gland
Strong lacZ expression is detectable in myocytes.
Female Reproductive Systems
Ovary
Few interstitial cells express lacZ moderately.
Oviduct/Uterus
LacZ expression is detectable in Fallopian tubules and in the myometrium.
Vagina/Cervix
Moderate to strong lacZ expression is detectable in ganglia.
No Expression:
LacZ expression is not detected in sciatic nerve, Harderian glands, thymus,
bone marrow, aorta, heart, lung, liver, gallbladder, pancreas, kidney, urinary
bladder, trachea, larynx, thyroid gland, adrenal glands, skeletal muscle and
skin.
:
Gene 799
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:
3 homozygous mutant females (136267, 145069, 147540)
3 homozygous mutant males (136241, 136256, 136258)
2 wild-type control females (136248, 136249)
2 wild-type control males (136244, 136257)
300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (147561, 147564)
2 homozygous mutant males (145060, 145061)
2 wild-type control females (147557, 147566)
2 wild-type control males (145057, 145058)
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:
When
compared to age- and gender-matched wild-type control mice at 300 days,
the homozygous males were found to have slightly reduced body body mass.
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, and/or differences of a nonspecific etiology. They are not considered
to be genotype related.
Gene 799
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 (136267, 145069, 147540)
3 homozygous mutant males (136241, 136256, 136258)
2 wild-type control females (136248, 136249)
2 wild-type control males (136244, 136257)
300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (147561, 147564)
2 homozygous mutant males (145060, 145061)
2 wild-type control females (147557, 147566)
2 wild-type control males (145057, 145058)
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 may have been present in some tissues. For example, mouse
136249 had pigment deposition in the spleen which correlates with the finding
of splenic discoloration at necropsy and a homozygous mutant mouse (147564) had
a systemic lymphoma. 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 799
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 (136267, 145069, 147540)
3 homozygous mutant males (136241, 136256, 136258)
2 wild-type control females (136248, 136249)
2 wild-type control males (136244, 136257)
300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (147561, 147564)
2 homozygous mutant males (145060, 145061)
2 wild-type control females (147557, 147566)
2 wild-type control males (145057, 145058)
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, kidney weight, kidneys, 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. For
example, mouse 136249 had splenic discoloration at necropsy which correlates
with the finding of pigment deposition in the spleen microscopically. 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:
At 49 days, all homozygous mutant mice had body weights that were slightly
lower than the age-matched and gender-matched wild-type control mice (female,
14%; males 11% on average). Liver weights and liver weight to body weight
ratios were also were slightly lower than the age-matched and gender-matched
wild-type control mice. At this time (49 days), these changes are not necessarily
considered to be related to genotype.
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 799
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 (136267, 181024, 181034)
3 homozygous mutant males (136241, 136258, 181060)
2 wild-type control females (136253, 140449)
2 wild-type control males (136259, 140444)
90 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (147547, 147561, 147564, 154354)
4 homozygous mutant males (145060, 145061, 159263, 190752)
4 wild-type control females (147549, 147557, 147566, 154355)
4 wild-type control males (145057, 145058, 159260, 190751)
180 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (147547, 147561, 147564, 154354)
4 homozygous mutant males (145060, 145061, 159263, 190752)
4 wild-type control females (147549, 147557, 147566, 154355)
4 wild-type control males (145057, 145058, 159260, 190751)
300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (147561, 147564)
2 homozygous mutant males (145060, 145061)
2 wild-type control females (147557, 147566)
2 wild-type control males (145057, 145058)
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 799
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 (136267, 145069, 147540)
3 homozygous mutant males (136256, 147533, 181058)
2 wild-type control females (136248, 136251)
2 wild-type control males (136259, 140445)
90 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (147561, 147564, 154354, 161206)
4 homozygous mutant males (145060, 145061, 159263, 190752)
4 wild-type control females (147549, 147557, 147566, 154355)
4 wild-type control males (145057, 145058, 159260, 190751)
180 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (147547, 147561, 147564, 154354)
4 homozygous mutant males (145060, 145061, 159263, 190752)
3 wild-type control females (147549, 147557, 154352)
4 wild-type control males (145057, 145058, 159260, 190751)
300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (147564, 178254)
2 homozygous mutant males (145060, 145061)
2 wild-type control females (147557, 147566)
2 wild-type control males (145057, 145058)
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 799
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 (136267, 145069, 147540)
3 homozygous mutant males (136241, 136256, 136258)
2 wild-type control females (136248, 136249)
2 wild-type control males (136244, 136257)
300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (147561, 147564)
2 homozygous mutant males (145060, 145061)
2 wild-type control females (147557, 147566)
2 wild-type control males (145057, 145058)
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 799
Aging Metrics
There
were no significant differences detected in the homozygous mutant animals when
compared with age- and gender-matched wild-type control mice.
Body
weights and body lengths were measured for mice at 49, 90, and 180 days of age.
49
Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (147547, 147561, 147564, 154354)
4 homozygous mutant males (145060, 145061, 159263, 190752)
4 wild-type control females (147549, 147557, 147566, 154355)
4 wild-type control males (145057, 145058, 159260, 190751)
90 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (147547, 147561, 147564, 154354)
4 homozygous mutant males (145060, 145061, 159263, 190752)
4 wild-type control females (147549, 147557, 147566, 154355)
4 wild-type control males (145057, 145058, 159260, 190751)
180 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (147547, 147561, 147564, 154354)
4 homozygous mutant males (145060, 145061, 159263, 190752)
4 wild-type control females (147549, 147557, 147566, 154355)
4 wild-type control males (145057, 145058, 159260, 190751)
300 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (147547, 147564, 154354)
5 homozygous mutant males (178248, 178251, 190749, 190750, 190752)
1 wild-type control female (154355)
Body Weight and Length Findings:
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.
Gene 799
Home Cage Observations
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 have home cage observations:
113 Day Cohort Mouse ID numbers are as
follows:
1 homozygous mutant male (213663)
Home cage observations are in-life observations collected by animal care
personnel over the lifetime of the mice. The observables are often
similar to those in the physical examination.
Home cage observation:
One male homozygous mutatnt male mouse
(213663) was observed to have clinical symptoms indicative of a seizure.
This could occur spontaneously in mice of this age group. Therefore,
we are not reporting these findings as phenotypic changes, but we present them
here for your consideration.