Gene: 460Name: Rgs2Family: G-Protein SignallingSubfamily: RGSAccession: U67187GI: 1911236

Gene 460
Summary of Phenotypic Analysis

There were no 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. 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:

  • Physical examination
  • Necropsy, including body length, body weight, and organ weight measurements
  • Histological examination of tissues and organs
  • Bone marrow section evaluation
  • Complete blood counts and differential cell counts
  • Clinical chemistry panels
  • Densitometry
  • Aging studies

There was a tendency toward decreased body weight at necropsy and mouse metrics, as well as decreased total tissue mass at densitometry, in some of the 49 and 300 day homozygous mutant females and males, although body weight and total tissue mass were also low in some wild-type mice. We have not reported these findings as phenotypic changes but we have presented them for your consideration.


 

Gene 460
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 (beta-galactosidase) expression is detectable in brain, heart, kidney, larynx, pituitary gland, salivary gland and male reproductive system.

Expression:
Brain
In wholemount staining lacZ expression is detectable in olfactory bulb, lateral septal nuclei, thalamus, cerebellum and brainstem. On coronal sections lacZ expression is detectable in lateral septal nuclei, thalamus and brainstem.

Heart
Weak lacZ expression is detectable in cardiomyocytes.
 
Kidney
LacZ expression is detectable in distinct tubules in the cortex. Very weak expression is detectable in the papilla.

Larynx
LacZ expression is detectable in submucosal glands.

Pituitary Gland
LacZ expression is detectable in pars distalis and pars intermedia.

Salivary Glands
Weak to moderate lacZ expression is detectable throughout the glands.

Male Reproductive Systems
Prostate and Ampullary Gland
Strong lacZ expression is detectable in many epithelial cells.

No Expression: 
LacZ expression is not detected in spinal cord, sciatic nerve, eyes, Harderian glands, thymus, spleen, lymph nodes, bone marrow, aorta, lung, liver, gallbladder, pancreas, urinary bladder, trachea, esophagus, thyroid gland, parathyroid gland, adrenal gland, tongue, skeletal muscle, skin, and female reproductive system.


 

Gene 460
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 (187114, 189668, 196737)
3 homozygous mutant males (196734, 199962, 199963)
2 wild-type control females (187110, 187112)
2 wild-type control males (196732, 199958)

300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (199966, 208784)
2 homozygous mutant males (209162, 222614)
2 wild-type control females (199967, 208790)

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 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 related to genotype.

Body and Organ Weight Findings:

When compared to age- and gender-matched wild-type mice, there was a tendency toward decreased body weight in one 49 day homozygous mutant female (187114), two 49 day homozygous mutant males (196734, 199962), two 300 day homozygous mutant females (199966, 208784) (although it was also low in wild-type female 208790), and one 300 day homozygous mutant male (222614). The findings correlate with the body weight tendencies observed at mouse metrics. We have not reported these findings as phenotypic changes but we have presented them 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 460
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 (187114, 189668, 196737)
3 homozygous mutant males (196734, 199962, 199963)
2 wild-type control females (187110, 187112)
2 wild-type control males (196732, 199958)

300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (199966, 208784)
1 homozygous mutant male (209162)

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, 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 are 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 460
Hematology

There were no significant differences 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.

49 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (187114, 189668, 196738, 196739)
2 homozygous mutant males (199962, 199963)
3 wild-type control females (187110, 187112, 187118)
2 wild-type control males (196732, 211311)

90 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (199966, 208784, 211314, 211315)
4 homozygous mutant males (209162, 222614, 260605, 268215)
4 wild-type control females (199967, 208790, 209140, 222619)
4 wild-type control males (240616, 240617, 240618, 272179)

180 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (199966, 208784, 211314, 211315)
2 homozygous mutant males (209162, 222614)
4 wild-type control females (199967, 208790, 209140, 222619)
3 wild-type control males (240616, 240617, 240618)

300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (199966, 208784)
2 homozygous mutant males (209162, 222614)
1 wild-type control female (208790)
2 wild-type control males (240616, 240617)

Although minor variations of hematological values were present in some animals, these changes were not related to genotype and, thus, were not considered phenotypically relevant.


 

Gene 460
Hematology

There were no significant differences 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.

49 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (187114, 189668, 196738, 196739)
2 homozygous mutant males (199962, 199963)
3 wild-type control females (187110, 187112, 187118)
2 wild-type control males (196732, 211311)

90 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (199966, 208784, 211314, 211315)
4 homozygous mutant males (209162, 222614, 260605, 268215)
4 wild-type control females (199967, 208790, 209140, 222619)
4 wild-type control males (240616, 240617, 240618, 272179)

180 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (199966, 208784, 211314, 211315)
2 homozygous mutant males (209162, 222614)
4 wild-type control females (199967, 208790, 209140, 222619)
3 wild-type control males (240616, 240617, 240618)

300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (199966, 208784)
2 homozygous mutant males (209162, 222614)
1 wild-type control female (208790)
2 wild-type control males (240616, 240617)

Although minor variations of hematological values were present in some animals, these changes were not related to genotype and, thus, were not considered phenotypically relevant.


 

Gene 460
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 (187114, 189668, 196737)
3 homozygous mutant males (196734, 199962, 199963)
2 wild-type control females (187110, 187112)
2 wild-type control males (196732, 199958)

300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (199966, 208784)
2 homozygous mutant males (209162, 222614)
2 wild-type control females (199967, 208790)
2 wild-type control males (240616, 240617)

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:

When compared to age- and gender-matched wild-type control mice, there is a tendency toward decreased total tissue mass in one 49 day homozygous mutant female (187114), two 49 day homozygous mutant males (196734, 199962), and four 300 day homozygous mutant females (199966, 208784) and males (209162, 222614) (although total tissue mass is also low in one wild-type female 208790). This variable is used for calculation and is not independent of body weight. We have not reported these findings as phenotypic changes, but we have presented them here for your consideration.

Other 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 460
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 (187114, 189668, 196737)
3 homozygous mutant males (196734, 199962, 199963)
2 wild-type control females (187110, 187112)
2 wild-type control males (196732, 199958)

300 Day Cohort Mouse ID numbers are as follows:
2 homozygous mutant females (199966, 208784)
2 homozygous mutant males (209162, 222614)
2 wild-type control females (199967, 208790)
2 wild-type control males (240616, 240617)

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, 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, 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 the appropriate gender.)

One 300 day homozygous mutant male (222614) was reported to be thin and hyperactive, findings that correlated with decreased body weight at necropsy. We have not reported these findings as phenotypic changes but have presented them for your consideration.

Other 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, procedural artifacts, and/or findings of a nonspecific etiology. However, none of these differences was regarded as biologically significant or genotype related.


 

Gene 460
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 (199966, 208784, 211314, 211315)
4 homozygous mutant males (209162, 222614, 260605, 268215)
5 wild-type control females (199967, 199969, 208790, 209140, 222619)
4 wild-type control males (240616, 240617, 240618, 272179)

90 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (199966, 208784, 211314, 211315)
4 homozygous mutant males (209162, 222614, 260605, 268215)
4 wild-type control females (199967, 208790, 209140, 222619)
4 wild-type control males (240616, 240617, 240618, 272179)

180 Day Cohort Mouse ID numbers are as follows:
4 homozygous mutant females (199966, 208784, 211314, 211315)
2 homozygous mutant males (209162, 222614)
4 wild-type control females (199967, 208790, 209140, 222619)
3 wild-type control males (240616, 240617, 240618)

300 Day Cohort Mouse ID numbers are as follows:
1 homozygous mutant female (208784)
1 homozygous mutant male (209162)
2 wild-type control females (208790, 209140)
3 wild-type control males (240616, 240617, 240618)

Body Weight and Length Findings:

When compared to age- and gender-matched wild-type control mice, there was a tendency towards decreased body weight in two 49 day homozygous mutant females (208784, 211315) (although two wild-type females 208790 and 222619 also have low body weight), two 49 day homozygous mutant males (222614, 260605),  one 90 day homozygous mutant female (208784)  (although two wild-type females 208790 and 222619 also have low body weight), two 90 day homozygous mutant males (222614, 260605), one 180 day homozygous mutant male (222614), and one 300 day homozygous mutant female (208784) (although one wild-type female 208790 also had low body weight). The findings correlate with the body weight tendencies observed at necropsy. We have not presented these findings as phenotypic changes but we have presented 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.