Gene: 1468Name: Fzd10Family: GPCRSubfamily: WNTAccession: NM_175284GI: 31341523

Gene 1468
Summary of Phenotypic Analysis

There were no significant differences detected in the homozygous mutant mice 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:

Gene 1468
Expression Summary

Taqman Summary:
The highest levels of RNA transcripts are detectable in urinary bladder, adrenal gland and uterus.

Moderate levels of RNA transcripts are detectable in: whole brain, cortex, subcortical region, cerebellum, brainstem, spinal cord, eye, thymus, lymph nodes, skin, gallbladder, pituitary gland, salivary gland, tongue, stomach, epididymis, coagulating gland, prostate gland, ovary and white fat.
      
Lower levels of RNA transcripts are also detectable in: olfactory bulb, Harderian glands, lung, liver, kidney, spleen, skeletal muscle, small intestine, large intestine, cecum, testis and seminal vesicle.

No RNA transcripts are detectable in heart, pancreas and bone marrow.

LacZ Summary:
Most striking lacZ expression was detected in the central nervous system and cervical epithelium.  In the brain very strong staining was observed in different structures, including brainstem, thalamus and ventricles.  Very strong, scattered staining was also detected throughout the spinal cord.  Staining was observed in different cell and tissue types, including neurons, epithelium, smooth muscle and blood vessels.

LacZ expression was detected in:  brain, spinal cord, eyes, kidney, skin, prostate gland, uterus and cervix.

LacZ expression was not detected in:  sciatic nerve, thymus, spleen, lymph nodes, bone marrow, aorta, heart, lung, liver, pancreas, urinary bladder, thyroid gland, larynx, pituitary gland, adrenal glands, skeletal muscle, testis, and ovary.


 

Gene 1468
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. The data were compiled from the N0F2 and N1F2 generations.

49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (326496, 339171, 343234)
3 homozygous mutant males (343236, 354167, 359055)
2 wild-type control females (326494, 341969)
3 wild-type control males (307472, 326500, 341965)

Bone Mineral Density (BMD in g/cm
2 ), 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:

Certain densitometric differences between mice, including low fat percentage, were present that occasionally occur spontaneously in this age group. In this target, small differences were present in the 49 day cohort in two homozygous mutant females (339171, 343234) and one homozygous mutant male (343236). Therefore, we have not reported this finding as a phenotypic change, but we have presented it 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 1468
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. The data were compiled from the N0F2 and N1F2 generations.

49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (326496, 339171, 343234)
3 homozygous mutant males (343236, 354167, 359055)
2 wild-type control females (326494, 341969)
3 wild-type control males (307472, 326500, 341965)

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, adrenal glands, 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 lesions, including bilateral moderate diffuse hypospermatogenesis in the testis and bilateral severe diffuse oligospermia in the epididymis, were present that occasionally occur spontaneously in mice of this sex and age group. In this target, such lesions were present in one 49 day homozygous mutant male (343236).  We have not reported these findings as phenotypic changes, but we have presented them here for your consideration.

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 1468
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. The data were compiled from the N0F2 and N1F2 generations.

49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (326496, 339171, 343234)
3 homozygous mutant males (343236, 354167, 359055)
2 wild-type control females (326494, 341969)
3 wild-type control males (307472, 326500, 341965)

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. For example, a 49 day cohort homozygous mutant female (339171) was reported to have a splenic nodule for which there was  a histopathological correlate of a small nodule of accessory splenic tissue. 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 1468
Clinical Chemistry

There were no significant differences 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 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 (326496, 339171, 343234)
3 homozygous mutant males (343236, 354167, 359055)
3 wild-type control females (326494, 341969, 341970)
4 wild-type control males (307472, 326500, 326502, 341965)

When compared to age- and gender-matched wild-type control mice, one of two homozygous mutant males (354167) had increased levels of Glucose. 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 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 1468
Hematology

There were no significant differences 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. The data were compiled from the N0F2 and N1F2 generations.

49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (326496, 339171, 343234)
3 homozygous mutant males (343236, 354167, 359055)
2 wild-type control females (326494, 341969)
3 wild-type control males (307472, 326500, 341965)

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 1468
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. The data were compiled from the N0F2 and N1F2 generations.

49 Day Cohort Mouse ID numbers are as follows:
3 homozygous mutant females (326496, 339171, 343234)
3 homozygous mutant males (343236, 354167, 359055)
2 wild-type control females (326494, 341969)
3 wild-type control males (307472, 326500, 341965)

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 homozygous 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.