Phenotypes associated with this allele

• Allele Symbol: Nr5a1^tm1Klp
• Allele Name: targeted mutation 1, Keith L Parker
• Allele ID: MGI:1857391
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nr5a1^tm1Klp/Nr5a1^tm1Klp	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:2180053
hm2	Nr5a1^tm1Klp/Nr5a1^tm1Klp	involves: 129P2/OlaHsd * C57BL/6 * FVB	MGI:2663049
ht3	Nr5a1^tm1Klp/Nr5a1^tm2Klp	involves: 129P2/OlaHsd	MGI:7280686
cn4	Amhr2^tm3(cre)Bhr/Amhr2^+ Nr5a1^tm1Klp/Nr5a1^tm2Klp	involves: 129P2/OlaHsd * 129S7/SvEvBrd	MGI:4361353

Genotype
MGI:2180053

hm1

• Allelic Composition: Nr5a1^tm1Klp/Nr5a1^tm1Klp
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:28763 )

• 16% of homozygotes survive for more than a month with corticosteroid intervention

postnatal lethality, complete penetrance ( J:35576 )

• animals die within 8 days of birth due to adrenal insufficiency

postnatal lethality, incomplete penetrance ( J:28763 )

• most untreated homozygotes die within 3 days of birth; one lived to 8 days of age; with daily corticosteroid treatment, 50% of null animals survive to weaning age

endocrine/exocrine glands

absent adrenal gland ( J:35576 )

• a consequence of apoptosis within the developing adrenal gland: apparent at E11.5

agonadal ( J:35576 )

• a consequence of apoptosis in both sexes: apparent in the genital ridge at E12

absent ovary ( J:35576 )

• females lacked ovaries

absent testes ( J:35576 )

• males lacked testes

reproductive system

abnormal primary sex determination ( J:35576 )

agonadal ( J:35576 )

• a consequence of apoptosis in both sexes: apparent in the genital ridge at E12

absent ovary ( J:35576 )

• females lacked ovaries

absent testes ( J:35576 )

• males lacked testes

secondary sex reversal ( J:35576 )

• genotypic males develop uteri, vagina and oviducts: apparent at E12

• external genitalia of genotypic males are female

embryo

abnormal gonadal ridge morphology ( J:35576 )

• apoptosis in both sexes: apparent in the genital ridge at E12

Genotype
MGI:2663049

hm2

• Allelic Composition: Nr5a1^tm1Klp/Nr5a1^tm1Klp
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB

nervous system

abnormal neuron differentiation ( J:83384 )

• expression of early and late ventromedial hypothalamic nucleus markers is altered indicating impaired terminal differentiation of ventromedial hypothalamic nucleus neurons

abnormal ventromedial hypothalamic nucleus morphology ( J:83384 )

• impaired terminal differentiation of ventromedial hypothalamic nucleus neurons

abnormal innervation ( J:83384 )

• neonates exhibit a loss of ventromedial hypothalamic nucleus projections to both the bed nucleus of stria terminalis and amygdala, but maintain limited projections to the anterior hypothalamus

cellular

abnormal neuron differentiation ( J:83384 )

• expression of early and late ventromedial hypothalamic nucleus markers is altered indicating impaired terminal differentiation of ventromedial hypothalamic nucleus neurons

Genotype
MGI:7280686

ht3

• Allelic Composition: Nr5a1^tm1Klp/Nr5a1^tm2Klp
• Genetic Background: involves: 129P2/OlaHsd

reproductive system

decreased ovary weight ( J:145805 )

♀ • adult ovaries weigh significantly less than those from wild-type controls (5.05 +/- 0.50 mg versus 7.39 +/- 0.52 mg)

ovary hypoplasia ( J:145805 )

♀ • adult females show mild ovarian hypoplasia

♀ • however, female fertility is not impaired and ovarian function is largely normal

decreased superovulation rate ( J:145805 )

♀ • 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

endocrine/exocrine glands

decreased ovary weight ( J:145805 )

♀ • adult ovaries weigh significantly less than those from wild-type controls (5.05 +/- 0.50 mg versus 7.39 +/- 0.52 mg)

ovary hypoplasia ( J:145805 )

♀ • adult females show mild ovarian hypoplasia

♀ • however, female fertility is not impaired and ovarian function is largely normal

Genotype
MGI:4361353

cn4

• Allelic Composition: Amhr2^tm3(cre)Bhr/Amhr2⁺; Nr5a1^tm1Klp/Nr5a1^tm2Klp
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd

reproductive system

absent corpus luteum ( J:91352 , J:145805 )

♀ (J:91352)

♀ (J:145805)

abnormal ovarian follicle number ( 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)

decreased primary ovarian follicle number ( J:145805 )

♀ • at P21, the number of primary follicles is significantly decreased

decreased primordial ovarian follicle number ( J:145805 )

♀ • at P21, the number of primordial follicles (the primordial follicle pool) is significantly decreased

♀ • decreased reserve of follicles persists into adulthood

decreased secondary ovarian follicle number ( J:145805 )

♀ • at P21, the number of small pre-antral follicles is significantly decreased

decreased tertiary ovarian follicle number ( J:145805 )

♀ • at P21, the number of antral follicles is significantly decreased

impaired ovarian folliculogenesis ( J:145805 )

♀ • 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

ovarian follicular cyst ( J:91352 )

♀ • the few remaining ovarian follicles contain hemorrhagic cysts

decreased ovary weight ( J:145805 )

♀ • adult ovaries weigh significantly less than those from wild-type controls (1.79 +/- 0.15 mg versus 7.39 +/- 0.52 mg)

ovary hypoplasia ( J:91352 , J:145805 )

♀ • 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)

abnormal seminiferous tubule morphology ( J:91352 )

♂ • in adult males, the lumens of the seminiferous tubules fail to open, suggesting impaired Sertoli cell secretion of fluid

abnormal testis development ( J:91352 )

♂ • 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

abnormal testis cord formation ( J:91352 )

♂ • at E14.5, testes display delayed organization of the testes cords

small testis ( J:91352 )

♂ • at E14.5 and E16.5, testes are significantly smaller than wild-type

testis hypoplasia ( J:91352 )

♂ • 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

cryptorchism ( J:91352 )

♂ • 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

abnormal ovary physiology ( J:145805 )

♀ • 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

ovary hemorrhage ( J:91352 )

♀ • the few remaining ovarian follicles contain hemorrhagic cysts

decreased granulosa cell proliferation ( J:145805 )

♀ • 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

abnormal uterus morphology ( J:145805 )

♀ • at 8-10 weeks of age, uterine histology revealed a reduction in epithelial, myometrial, and stromal layers

abnormal endometrial gland morphology ( J:145805 )

♀ • the glandular elements of the endometrial layer appear less complex

abnormal endometrial gland development ( J:145805 )

♀ • endometrial glands exhibit a less differentiated glandular structure than in control uteri

decreased endometrial gland number ( J:145805 )

♀ • only a few scattered endometrial glands are detected in the stroma

thin myometrium ( J:145805 )

♀

decreased uterus weight ( J:145805 )

♀ • at 8-10 weeks of age, uterine weight is significantly lower than in control females

arrest of spermatogenesis ( J:91352 )

♂ • spermatogonia fail to develop into mature sperm

internal male genitalia hypoplasia ( J:91352 )

♂ • male mice display significantly hypoplastic internal genitalia

absent sexual maturation ( J:91352 )

• both male and female mice display no postnatal sexual maturation

• however, both male and female mice exhibit normal external genitalia at birth

abnormal ovulation ( J:91352 )

♀ • absence of corpora lutea indicates impaired ovulation

decreased superovulation rate ( J:145805 )

♀ • 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 Nr5a1^tm2Klp allele but negative for the Amhr2^tm3(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

abnormal estrous cycle ( J:145805 )

♀ • estrous cycles range from abnormally prolonged cycles (50%) to complete acyclicity (50%)

short estrus ( J:145805 )

♀ • when observed, estrous phase length is significantly shorter than in control females

absent estrous cycle ( J:145805 )

♀ • 50% of females are completely acyclic

prolonged estrous cycle ( J:145805 )

♀ • 50% of females show abnormally prolonged cycles

female infertility ( J:91352 , J:145805 )

♀ • 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)

male infertility ( J:91352 )

♂ • male mice are sterile

endocrine/exocrine glands

small adrenal glands ( J:91352 )

• adrenal glands are smaller than wild-type but appear histologically intact

abnormal endometrial gland morphology ( J:145805 )

♀ • the glandular elements of the endometrial layer appear less complex

abnormal endometrial gland development ( J:145805 )

♀ • endometrial glands exhibit a less differentiated glandular structure than in control uteri

decreased endometrial gland number ( J:145805 )

♀ • only a few scattered endometrial glands are detected in the stroma

absent corpus luteum ( J:91352 , J:145805 )

♀ (J:91352)

♀ (J:145805)

abnormal ovarian follicle number ( 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)

decreased primary ovarian follicle number ( J:145805 )

♀ • at P21, the number of primary follicles is significantly decreased

decreased primordial ovarian follicle number ( J:145805 )

♀ • at P21, the number of primordial follicles (the primordial follicle pool) is significantly decreased

♀ • decreased reserve of follicles persists into adulthood

decreased secondary ovarian follicle number ( J:145805 )

♀ • at P21, the number of small pre-antral follicles is significantly decreased

decreased tertiary ovarian follicle number ( J:145805 )

♀ • at P21, the number of antral follicles is significantly decreased

impaired ovarian folliculogenesis ( J:145805 )

♀ • 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

ovarian follicular cyst ( J:91352 )

♀ • the few remaining ovarian follicles contain hemorrhagic cysts

decreased ovary weight ( J:145805 )

♀ • adult ovaries weigh significantly less than those from wild-type controls (1.79 +/- 0.15 mg versus 7.39 +/- 0.52 mg)

ovary hypoplasia ( J:91352 , J:145805 )

♀ • 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)

abnormal seminiferous tubule morphology ( J:91352 )

♂ • in adult males, the lumens of the seminiferous tubules fail to open, suggesting impaired Sertoli cell secretion of fluid

abnormal testis development ( J:91352 )

♂ • 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

abnormal testis cord formation ( J:91352 )

♂ • at E14.5, testes display delayed organization of the testes cords

small testis ( J:91352 )

♂ • at E14.5 and E16.5, testes are significantly smaller than wild-type

testis hypoplasia ( J:91352 )

♂ • 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

cryptorchism ( J:91352 )

♂ • 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

abnormal ovary physiology ( J:145805 )

♀ • 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

ovary hemorrhage ( J:91352 )

♀ • the few remaining ovarian follicles contain hemorrhagic cysts

decreased granulosa cell proliferation ( J:145805 )

♀ • 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

homeostasis/metabolism

decreased circulating testosterone level ( J:91352 )

• adult males exhibit plasma testosterone levels that are indistinguishable from those of prepubertal wild-type males

decreased circulating estradiol level ( J:145805 )

♀ • 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

increased circulating follicle stimulating hormone level ( J:145805 )

♀ • basal plasma FSH levels are significantly higher than in wild-type females

growth/size/body

ovarian follicular cyst ( J:91352 )

♀ • the few remaining ovarian follicles contain hemorrhagic cysts

cellular

decreased granulosa cell proliferation ( J:145805 )

♀ • 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

cardiovascular system

ovary hemorrhage ( J:91352 )

♀ • the few remaining ovarian follicles contain hemorrhagic cysts