Analysis Tools
normal phenotype
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• homozygotes are phenotypically normal and fertile
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Allele Symbol Allele Name Allele ID |
Nr5a1tm2Klp targeted mutation 2, Keith L Parker MGI:2180013 |
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| Summary |
6 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• homozygotes are phenotypically normal and fertile
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• adult ovaries weigh significantly less than those from wild-type controls (5.05 +/- 0.50 mg versus 7.39 +/- 0.52 mg)
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• adult females show mild ovarian hypoplasia
• however, female fertility is not impaired and ovarian function is largely normal
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• following gonadotropin-induced ovulation, 8- to 12-wk-old females ovulate an average of 23.3 +/- 5.1 oocytes per female versus 35.3 +/- 2.9 oocytes per female in wild-type controls
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• adult ovaries weigh significantly less than those from wild-type controls (5.05 +/- 0.50 mg versus 7.39 +/- 0.52 mg)
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• adult females show mild ovarian hypoplasia
• however, female fertility is not impaired and ovarian function is largely normal
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• zone is disorganized with pleomorphic nuclei, whereas inner zona fasciculata appears normal in young and old mice
• cells in the zona granulosa dedifferentiated with Nr5a1 deletion
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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(J:91352)
(J:145805)
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• adult ovaries show a reduction in the total number of ovarian follicles
(J:91352)
• at P21 (just before the initiation of puberty), the number of growing follicles as well as the total number of follicles is significantly reduced
(J:145805)
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• at P21, the number of primary follicles is significantly decreased
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• at P21, the number of primordial follicles (the primordial follicle pool) is significantly decreased
• decreased reserve of follicles persists into adulthood
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• at P21, the number of small pre-antral follicles is significantly decreased
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• at P21, the number of antral follicles is significantly decreased
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• adult ovaries exhibit the normal range of follicles up to the preovulatory stage but no corpora lutea, suggesting a defect in the final steps of folliculogenesis and/or ovulation
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• the few remaining ovarian follicles contain hemorrhagic cysts
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• adult ovaries weigh significantly less than those from wild-type controls (1.79 +/- 0.15 mg versus 7.39 +/- 0.52 mg)
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• adult ovaries are normally positioned adjacent to the oviducts but appear hypoplastic
(J:91352)
• however, at E14.5 and E16.5, ovaries and internal genital structures show no differences in size or histology relative to wild-type ovaries
(J:91352)
(J:145805)
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• in adult males, the lumens of the seminiferous tubules fail to open, suggesting impaired Sertoli cell secretion of fluid
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• at E14.5, testes are located adjacent to the kidneys but are significantly smaller and do not contain distinct testes cords
• at E16.5, testes remain smaller than wild-type testes but have organized into testicular cords
• delayed testis development is associated with decreased Leydig cell expression of essential components of testosterone biosynthesis
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• at E14.5, testes display delayed organization of the testes cords
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• at E14.5 and E16.5, testes are significantly smaller than wild-type
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• adult male mice display significantly hypoplastic testes
• at E14.5 and E16.5, decreased testis size is associated with reduced cell proliferation in somatic cells of the testes
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• testes remain at the level of the bladder within the abdominal cavity
• however, no structures derived from the Mullerian ducts (such as oviducts or uterus) are observed
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• adult ovaries show significantly reduced basal and eCG-stimulated expression of Amh (anti-Mullerian hormone) as well as decreased eCG-induced ovarian expression of aromatase (Cyp19a1) and cyclin D2 (Ccnd2) relative to control ovaries
• in contrast, ovaries exhibit increased basal expression of Inha (inhibin-alpha) but -- unlike control ovaries -- fail to show increased Inha expression in response to eCG stimulation
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• the few remaining ovarian follicles contain hemorrhagic cysts
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• granulosa cells of growing follicles show significantly reduced expression of CCND2 (cyclin D2) and MKI67 (Ki67) but increased expression of CDKN1B (p27), suggesting impaired granulosa cell proliferation
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• at 8-10 weeks of age, uterine histology revealed a reduction in epithelial, myometrial, and stromal layers
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• the glandular elements of the endometrial layer appear less complex
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• endometrial glands exhibit a less differentiated glandular structure than in control uteri
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• only a few scattered endometrial glands are detected in the stroma
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• at 8-10 weeks of age, uterine weight is significantly lower than in control females
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• spermatogonia fail to develop into mature sperm
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• male mice display significantly hypoplastic internal genitalia
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• both male and female mice display no postnatal sexual maturation
• however, both male and female mice exhibit normal external genitalia at birth
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• absence of corpora lutea indicates impaired ovulation
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• after gonadotropin-induced ovulation, 8- to 12-wk-old females ovulate an average of only 1.0 +/- 0.7 oocytes per female versus 35.3 +/- 2.9 oocytes per female in wild-type controls (i.e. females heterozygous for the Nr5a1tm2Klp allele but negative for the Amhr2tm3(cre)Bhr allele)
• following superovulation induction, 80% of females had no oocytes retrieved from the oviducts; 2 females released 3 and 4 oocytes each, some found in immature stages of development
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• estrous cycles range from abnormally prolonged cycles (50%) to complete acyclicity (50%)
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• when observed, estrous phase length is significantly shorter than in control females
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• 50% of females are completely acyclic
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• 50% of females show abnormally prolonged cycles
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• female mice are sterile
(J:91352)
• when mated with young wild-type male mice, no adult females delivered any pups during a >1 yr observation period
(J:145805)
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• male mice are sterile
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• adrenal glands are smaller than wild-type but appear histologically intact
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• the glandular elements of the endometrial layer appear less complex
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• endometrial glands exhibit a less differentiated glandular structure than in control uteri
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• only a few scattered endometrial glands are detected in the stroma
|
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|
(J:91352)
(J:145805)
|
|
|
• adult ovaries show a reduction in the total number of ovarian follicles
(J:91352)
• at P21 (just before the initiation of puberty), the number of growing follicles as well as the total number of follicles is significantly reduced
(J:145805)
|
|
|
• at P21, the number of primary follicles is significantly decreased
|
|
|
• at P21, the number of primordial follicles (the primordial follicle pool) is significantly decreased
• decreased reserve of follicles persists into adulthood
|
|
|
• at P21, the number of small pre-antral follicles is significantly decreased
|
|
|
• at P21, the number of antral follicles is significantly decreased
|
|
|
• adult ovaries exhibit the normal range of follicles up to the preovulatory stage but no corpora lutea, suggesting a defect in the final steps of folliculogenesis and/or ovulation
|
|
|
• the few remaining ovarian follicles contain hemorrhagic cysts
|
|
|
• adult ovaries weigh significantly less than those from wild-type controls (1.79 +/- 0.15 mg versus 7.39 +/- 0.52 mg)
|
|
|
• adult ovaries are normally positioned adjacent to the oviducts but appear hypoplastic
(J:91352)
• however, at E14.5 and E16.5, ovaries and internal genital structures show no differences in size or histology relative to wild-type ovaries
(J:91352)
(J:145805)
|
|
|
• in adult males, the lumens of the seminiferous tubules fail to open, suggesting impaired Sertoli cell secretion of fluid
|
|
|
• at E14.5, testes are located adjacent to the kidneys but are significantly smaller and do not contain distinct testes cords
• at E16.5, testes remain smaller than wild-type testes but have organized into testicular cords
• delayed testis development is associated with decreased Leydig cell expression of essential components of testosterone biosynthesis
|
|
|
• at E14.5, testes display delayed organization of the testes cords
|
|
|
• at E14.5 and E16.5, testes are significantly smaller than wild-type
|
|
|
• adult male mice display significantly hypoplastic testes
• at E14.5 and E16.5, decreased testis size is associated with reduced cell proliferation in somatic cells of the testes
|
|
|
• testes remain at the level of the bladder within the abdominal cavity
• however, no structures derived from the Mullerian ducts (such as oviducts or uterus) are observed
|
|
|
• adult ovaries show significantly reduced basal and eCG-stimulated expression of Amh (anti-Mullerian hormone) as well as decreased eCG-induced ovarian expression of aromatase (Cyp19a1) and cyclin D2 (Ccnd2) relative to control ovaries
• in contrast, ovaries exhibit increased basal expression of Inha (inhibin-alpha) but -- unlike control ovaries -- fail to show increased Inha expression in response to eCG stimulation
|
|
|
• the few remaining ovarian follicles contain hemorrhagic cysts
|
|
|
• granulosa cells of growing follicles show significantly reduced expression of CCND2 (cyclin D2) and MKI67 (Ki67) but increased expression of CDKN1B (p27), suggesting impaired granulosa cell proliferation
|
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• adult males exhibit plasma testosterone levels that are indistinguishable from those of prepubertal wild-type males
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• in response to eCG stimulation, 8-12-wk-old females show a significantly blunted increase in plasma estradiol levels relative to control females
• however, basal plasma estradiol levels are normal
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• basal plasma FSH levels are significantly higher than in wild-type females
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• the few remaining ovarian follicles contain hemorrhagic cysts
|
|
|
• granulosa cells of growing follicles show significantly reduced expression of CCND2 (cyclin D2) and MKI67 (Ki67) but increased expression of CDKN1B (p27), suggesting impaired granulosa cell proliferation
|
|
|
• the few remaining ovarian follicles contain hemorrhagic cysts
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
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• similar to that observed in mice that are heterozygous for Nr5a1tm2Klp and Nr5a1tm2.1Klp and hemizygous for Tg(Cga-cre)3Sac
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• similar to that observed in mice that are heterozygous for Nr5a1tm2Klp and Nr5a1tm2.1Klp and hemizygous for Tg(Cga-cre)3Sac
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• neither large preovulatory follicles nor corpora lutea are observed, similar to mice that are heterozygous for Nr5a1tm2Klp and Nr5a1tm2.1Klp and hemizygous for Tg(Cga-cre)3Sac
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• mutant mice display absence of follicular maturation beyond the antral stage
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• although mutant ovaries are smaller than wild-type, they are significantly larger than those of mice that are heterozygous for Nr5a1tm2Klp and Nr5a1tm2.1Klp and hemizygous for Tg(Cga-cre)3Sac
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• at 8 weeks of age, the weight of mutant ovaries (0.06 g/kg) is significantly lower than wild-type (0.47 g/kg), but higher than that of mice which are heterozygous for Nr5a1tm2Klp and Nr5a1tm2.1Klp and hemizygous for Tg(Cga-cre)3Sac (0.01 g/kg)
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• at 8 weeks of age, mutant interstitial Leydig cells are severely hypoplastic
• in contrast, Sertoli cells and developing germ cells (including mature sperm) are relatively intact
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• although mutant testes are smaller than wild-type, they are significantly larger than those of mice that are heterozygous for Nr5a1tm2Klp and Nr5a1tm2.1Klp and hemizygous for Tg(Cga-cre)3Sac
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• at 8 weeks of age, the weight of mutant testes (3.7 g/kg) is significantly lower than wild-type (7.9 g/kg), but significantly higher than that of mice which are heterozygous for Nr5a1tm2Klp and Nr5a1tm2.1Klp and hemizygous for Tg(Cga-cre)3Sac (0.4 g/kg)
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• similar to that observed in mice that are heterozygous for Nr5a1tm2Klp and Nr5a1tm2.1Klp and hemizygous for Tg(Cga-cre)3Sac
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• both male and female mutants show a milder degree of (hypomorphic) hypogonadism than mice that are heterozygous for Nr5a1tm2Klp and Nr5a1tm2.1Klp and hemizygous for Tg(Cga-cre)3Sac
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• both male and female mutants show little evidence for secondary sexual maturation
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• similar to that observed in mice that are heterozygous for Nr5a1tm2Klp and Nr5a1tm2.1Klp and hemizygous for Tg(Cga-cre)3Sac
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• similar to that observed in mice that are heterozygous for Nr5a1tm2Klp and Nr5a1tm2.1Klp and hemizygous for Tg(Cga-cre)3Sac
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• neither large preovulatory follicles nor corpora lutea are observed, similar to mice that are heterozygous for Nr5a1tm2Klp and Nr5a1tm2.1Klp and hemizygous for Tg(Cga-cre)3Sac
|
|
|
• mutant mice display absence of follicular maturation beyond the antral stage
|
|
|
• although mutant ovaries are smaller than wild-type, they are significantly larger than those of mice that are heterozygous for Nr5a1tm2Klp and Nr5a1tm2.1Klp and hemizygous for Tg(Cga-cre)3Sac
|
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• at 8 weeks of age, the weight of mutant ovaries (0.06 g/kg) is significantly lower than wild-type (0.47 g/kg), but higher than that of mice which are heterozygous for Nr5a1tm2Klp and Nr5a1tm2.1Klp and hemizygous for Tg(Cga-cre)3Sac (0.01 g/kg)
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• at 8 weeks of age, mutant interstitial Leydig cells are severely hypoplastic
• in contrast, Sertoli cells and developing germ cells (including mature sperm) are relatively intact
|
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|
• although mutant testes are smaller than wild-type, they are significantly larger than those of mice that are heterozygous for Nr5a1tm2Klp and Nr5a1tm2.1Klp and hemizygous for Tg(Cga-cre)3Sac
|
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|
• at 8 weeks of age, the weight of mutant testes (3.7 g/kg) is significantly lower than wild-type (7.9 g/kg), but significantly higher than that of mice which are heterozygous for Nr5a1tm2Klp and Nr5a1tm2.1Klp and hemizygous for Tg(Cga-cre)3Sac (0.4 g/kg)
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• mutant mice of both sexes show circulating FSH levels (4.5 ng/ml males, 5.2 ng/ml females) that are intermediate between those of wild-type mice (31.35 ng/ml males, 12.4 ng/ml females) and mice that are heterozygous for Nr5a1tm2Klp and Nr5a1tm2.1Klp and hemizygous for Tg(Cga-cre)3Sac (1.2 ng/ml males, 2.7 ng/ml females)
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• mutant males display a severe reduction in circulating LH levels similar to that observed in mice that are heterozygous for Nr5a1tm2Klp and Nr5a1tm2.1Klp and hemizygous for Tg(Cga-cre)3Sac
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• mutants do not engage in sexual activity
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• treatment with exogenous gonadotropins stimulated enlargement of the hypoplastic prostate glands
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• treatment with exogenous gonadotropins stimulated enlargement of the hypoplastic seminal vesicles
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• although ovarian follicles develop through the primary, secondary and antral stages, no large preovulatory follicles or corpora lutea are observed
• treatment with exogenous gonadotropins (PMSG) stimulated maturation of ovarian follicles to the preovulatory stage and induced ovulation, as indicated by the presence of corpora lutea
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• severe
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• mutant Leydig cells display none of the histological features typical of steroidogenic cells
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• interstitial Leydig cells are severely reduced in number
• treatment with exogenous gonadotropins stimulated Leydig cell hypertrophy and induced luminal opening of the seminiferous tubules
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• severe
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• mutant males have cryptorchid testes
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• male germ cells are significantly reduced in number
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• although ovarian follicles develop through the primary, secondary and antral stages, no large preovulatory follicles or corpora lutea are observed
• treatment with exogenous gonadotropins (PMSG) stimulated maturation of ovarian follicles to the preovulatory stage and induced ovulation, as indicated by the presence of corpora lutea
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• treatment with exogenous gonadotropins (PMSG) stimulated a significant increase in uterine size and development of the endometrial glands
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• mutant males fail to progress through the normal stages of spermatogenesis: occasional pachytene spermatocytes are observed, but mature spermatids are absent
• treatment with exogenous gonadotropins (PMSG) stimulated gonadal steroidogenesis, inducing maturation of spermatogonial precursors to the round spermatid stage
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• no mature spermatids are observed
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• mutant males show hypoplastic external and internal genitalia
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• treatment with exogenous gonadotropins stimulated enlargement of the hypoplastic prostate glands
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• treatment with exogenous gonadotropins stimulated enlargement of the hypoplastic seminal vesicles
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• mutant Leydig cells display none of the histological features typical of steroidogenic cells
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• interstitial Leydig cells are severely reduced in number
• treatment with exogenous gonadotropins stimulated Leydig cell hypertrophy and induced luminal opening of the seminiferous tubules
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• mutant males have cryptorchid testes
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• mutant gonads are severely hypoplastic
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• severe
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• severe
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• mutant vaginas fail to open at the normal age of puberty
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• both male and female mutants are viable but fail to show signs of secondary sexual maturation, even at 6 months of age
• both male and female mutants exhibit sexual infantilism of the accessory sex organs
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• although mutant pituitaries appear histologically intact, immunoreactive FSH leves are virtually undetectable
• in contrast, pituitary ACTH, TSH and prolactin levels are comparable to those in wild-type pituitaries
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• serum FSH levels are significantly reduced in both male and female mutants relative to wild-type controls
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• although mutant pituitaries appear histologically intact, immunoreactive LH leves are virtually undetectable
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• serum LH levels are significantly reduced in male mutants relative to wild-type controls
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• no mature spermatids are observed
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• male germ cells are significantly reduced in number
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| hypogonadotropic hypogonadism | DOID:0090070 |
OMIM:PS147950 |
J:66593 | |
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/23/2024 MGI 6.23 |
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