Gene: 753 | Name: Ppm1g | Family: Phosphatase | Subfamily: Serine/Threonine Phosp... | Accession: U42383 | GI: 3318654 |
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Gene 753
Summary of Phenotypic Analysis
Changes related to genotype:
There were no other significant differences detected in the homozygous and heterozygous mutant mice when compared with age- and gender-matched wild-type control mice.
Weaned progeny from the heterozygous matings were
genotyped. Fewer than expected homozygous mutant mice were identified by
PCR, when compared with observed numbers of wild-type and
heterozygous mutant mice. The genotypic ratio suggested a perinatal lethal
phenotype.
ES cells derived from the 129/ mouse substrain were used to generate chimeric mice. F1 mice were generated by breeding with C57BL/6 females. F2 mutant mice were produced by intercrossing F1 heterozygous males and females.
Wild-type control mice and homozygous and heterozygous mutant mice were evaluated by the following examinations or tests:
Gene
753
Behavior
Heterozygous
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, Startle response/PPI test, Tail flick test, Hot plate test, and
Metrazol test.
Mouse ID numbers are as follows for the N1 generation:
10 heterozygous mutant males (368950, 368951, 368952, 372510, 372511, 376357,
376358, 376359, 376360, 376378)
26 wild-type control males (365880, 366281, 368805, 368819, 368953, 369533,
370412, 370696, 370702, 370703, 372236, 372508, 372509, 372599, 374965, 375575,
375576, 375761, 375797, 375803, 376376, 376410, 376508, 376918, 377403, 379074)
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 heterozygous mutant mice were produced by
intercrossing F1N1 heterozygous males and females.
Behavior Findings:
When compared to age- and gender-matched wild-type control mice, heterozygous
mutant mice exhibited a significant decrease in prepulse inhibition,
indicating a stimulus processing deficit similar to that observed in some human
schizophrenic patients.
There
were no other genotype-related differences noted between heterozygous mutant
and wild-type control mice for any other parameters evaluated during behavior
testing.
Gene 753
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.
LacZ Summary:
LacZ expression was detected in all organs examined. Staining was
observed in different tissue and cell types, including smooth, cardiac and
skeletal muscle, epithelium, neurons, cartilage, lymphatic tissue, adipose
tissue and blood vessels.
LacZ expression was detected
in: brain, spinal cord, sciatic nerve, eyes, thymus, spleen, lymph nodes,
bone marrow, aorta, heart, lung, liver, pancreas, kidney, urinary bladder,
thyroid gland, larynx, pituitary gland, adrenal glands, skeletal muscle, skin,
testis, prostate gland, ovary, uterus and cervix.
Gene 753
Densitometry
There were no significant differences detected in the homozygous and
heterozygous mutant mice when compared with age- and gender-matched wild-type
control mice.
The following mice were evaluated by dual-energy x-ray absorptiometry. The data were compiled from the N0F2 and N1F2 generations.
49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (325301, 331037, 352263)
3 homozygous mutant males (331045, 335143, 335144)
3 heterozygous mutant females (323313, 323314, 325300)
3 heterozygous mutant males (323311, 323312, 323315)
2 wild-type control females (313585, 313586)
2 wild-type control males (313587, 313592)
Bone Mineral Density (BMD in g/cm2
), fat % (fat percentage 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:
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 753
Histopathology
There were no significant differences detected in the homozygous and heterozygous mutant mice when compared with age- and gender-matched wild-type control mice.
Tissues from the following mice were evaluated histologically. The data were compiled from the N0F2 and N1F2 generations.
49
Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (325301, 331037, 352263)
3 homozygous mutant males (331045, 335143, 335144)
3 heterozygous mutant females (323313, 323314, 325300)
3 heterozygous mutant males (323311, 323312, 323315)
2 wild-type control females (313585, 313586)
2 wild-type control males (313587, 313592)
No Significant Abnormalities:
The following tissues were examined and considered to have no genotype-related abnormality: brain, pituitary gland, ears, nasal cavity, salivary glands, oral cavity, lymph nodes, aorta, lungs, liver, 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 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.
Gene 753
Necropsy
There were no significant differences detected in the homozygous and heterozygous 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. The
data were compiled from the N0F2 and N1F2 generations.
49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (325301, 331037, 352263)
3 homozygous mutant males (331045, 335143, 335144)
3 heterozygous mutant females (323313, 323314, 325300)
3 heterozygous mutant males (323311, 323312, 323315)
2 wild-type control females (313585, 313586)
2 wild-type control males (313587, 313592)
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 the 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. 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 related to genotype.
Body and Organ Weight Findings:
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 753
Clinical Chemistry
There
were no significant differences in the homozygous or heterozygous mutant mice
when compared with age- and gender-matched wild-type control mice.
Serum
samples from the following mice were evaluated by a clinical chemistry panel.
The data were compiled from the N0F2 and N1F2 generations.
49
Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (325301, 331037, 352263)
3 homozygous mutant males (331045, 335143, 345935)
3 heterozygous mutant females (323313, 323314, 325300)
3 heterozygous mutant males (323311, 323312, 323315)
2 wild-type control females (313585, 313586)
2 wild-type control males (313587, 313593)
When compared to age- and gender-matched wild-type control mice, one homozygous
female (352263) had increase level of Blood Urea Nitrogen. We are not reporting
these findings as phenotypic changes, but we present them here for your
consideration.
Values for the other various analytes evaluated were generally similar between
homozygous or heterozygous mutant and wild-type control mice. Although
variations in clinical chemistry values were present in some mice, they were
not related to genotype and, thus, were not considered phenotypically relevant.
Gene 753
Hematology
There
were no significant differences in the homozygous or heterozygous 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. The data are compiled from the F2N0 and F2N1
generations.
49
Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (325301, 331037, 376362)
3 homozygous mutant males (331045, 335143, 335144)
3 heterozygous mutant females (323313, 323314, 325300)
3 heterozygous mutant males (323311, 323312, 323315)
2 wild-type control females (313583, 313585)
2 wild-type control males (313587, 313593)
Although minor variations of hematological values were present in some mice,
these changes were not related to genotype and, thus, were not considered
phenotypically relevant.
Gene 753
Physical Examination
There
were no significant differences detected in the homozygous and
heterozygous mutant mice when compared with age- and gender-matched
wild-type control mice.
The
following mice were evaluated by physical examination. The data were
compiled from the N0F2 and N1F2 generations.
49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (325301, 331037, 352263)
3 homozygous mutant males (331045, 335143, 335144)
3 heterozygous mutant females (323313, 323314, 325300)
3 heterozygous mutant males (323311, 323312, 323315)
2 wild-type control females (313585, 313586)
2 wild-type control males (313587, 313592)
Mice were examined in detail as follows: 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, 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, mice in cage,
respiration, skin appearance, snout, swelling - joints, tail, teeth color,
teeth length, urine, and whiskers. (Gender-specific observables apply to the
appropriate gender.)
Individual
mutant mice had only occasional minor differences in observed physical features
compared to wild-type control mice. These findings were 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 were
regarded as biologically significant or genotype related.