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Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Donor Strain 129P2/OlaHsd via E14TG2a ES cell line Generation N9F2pN1 Donating Investigator Eva Eicher, The Jackson Laboratory Description
Mice homozygous for this floxed allele are viable and fertile. These mutant mice have loxP sites flanking the C-terminal coding exon. When bred to Cre-recombinase expressing mice, offspring will have a deletion of this exon in the cre expressing tissue(s). These floxed mice may be useful in studying steroidogenic factors and pituitary gonadotrope function.For example, when crossed to a strain expressing Cre recombinase in the anterior and intermediate lobes of the pituitary gland (see Stock No. 004426), this mutant mouse strain may be useful in studies of pituitary gonadotrope function.
Development
A targeting vector was designed to place a loxP site upstream, and a loxP site and neomycin resistance cassette downstream of the C-terminal coding exon of the targted gene. The construct was electroporated into 129P2/OlaHsd-derived E14TG2a embryonic stem (ES) cells. Following blastocyst injection of correctly targeted ES cells, chimeric mice transmitted this "floxed" allele to produce mutant mice. These mutant mice have been backcrossed for at least 9 generations to DBA/2J inbred mice (Stock No. 000671).
| Control | ||
|---|---|---|
| 000671 DBA/2J | ||
| Considerations for Choosing Controls | ||
Strains carrying Nr5a1tm2Klp allele
007041 B6Ei.129P2-Nr5a1tm2Klp/EiJ View Strains carrying Nr5a1tm2Klp (1 strain)
Strains carrying other alleles of Nr5a1
003219 D2.129P2(B6)-Nr5a1tm1Klp/EiJ 006364 FVB-Tg(Nr5a1-cre)2Lowl/J View Strains carrying other alleles of Nr5a1 (2 strains)
Cre-lox Systems
View Related Disease (OMIM) Terms
Related Disease (OMIM) Terms
Hypogonadotropic Hypogonadism - Models with phenotypic similarity to human disease where etiologies are distinct.2
2 Human genes are associated with this disease. Orthologs of those genes do not appear in the mouse genotype(s).
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Nr5a1tm2Klp/Nr5a1tm2Klp
involves: 129P2/OlaHsd
- normal phenotype
- no abnormal phenotype detected (MGI Ref ID J:66593)
- homozygotes are phenotypically normal and fertile
The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services jaxservices@jax.org for customized breeding options.Nr5a1tm2Klp/Nr5a1tm2.1Klp Tg(Cga-cre)3Sac/0
involves: 129P2/OlaHsd * C57BL/6J * SJL (conditional)
- endocrine/exocrine gland phenotype
- abnormal Leydig cell morphology (MGI Ref ID J:66593)
- mutant Leydig cells display none of the histological features typical of steroidogenic cells
- Leydig cell hypoplasia (MGI Ref ID J:66593)
- interstitial Leydig cells are severely reduced in number
- treatment with exogenous gonadotropins stimulated Leydig cell hypertrophy and induced luminal opening of the seminiferous tubules
- absent corpus luteum (MGI Ref ID J:66593)
- absent mature ovarian follicles (MGI Ref ID J:66593)
- 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
- cryptorchism (MGI Ref ID J:66593)
- mutant males have cryptorchid testes
- ovary hypoplasia (MGI Ref ID J:66593)
- severe
- prostate gland hypoplasia (MGI Ref ID J:66593)
- treatment with exogenous gonadotropins stimulated enlargement of the hypoplastic prostate glands
- seminal gland hypoplasia (MGI Ref ID J:66593)
- treatment with exogenous gonadotropins stimulated enlargement of the hypoplastic seminal vesicles
- testicular hypoplasia (MGI Ref ID J:66593)
- severe
- reproductive system phenotype
- abnormal female reproductive anatomy (MGI Ref ID J:66593)
- absent corpus luteum (MGI Ref ID J:66593)
- absent mature ovarian follicles (MGI Ref ID J:66593)
- 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
- ovary hypoplasia (MGI Ref ID J:66593)
- severe
- uterine hypoplasia (MGI Ref ID J:66593)
- treatment with exogenous gonadotropins (PMSG) stimulated a significant increase in uterine size and development of the endometrial glands
- abnormal male reproductive anatomy (MGI Ref ID J:66593)
- mutant males show hypoplastic external and internal genitalia
- abnormal Leydig cell morphology (MGI Ref ID J:66593)
- mutant Leydig cells display none of the histological features typical of steroidogenic cells
- Leydig cell hypoplasia (MGI Ref ID J:66593)
- interstitial Leydig cells are severely reduced in number
- treatment with exogenous gonadotropins stimulated Leydig cell hypertrophy and induced luminal opening of the seminiferous tubules
- cryptorchism (MGI Ref ID J:66593)
- mutant males have cryptorchid testes
- prostate gland hypoplasia (MGI Ref ID J:66593)
- treatment with exogenous gonadotropins stimulated enlargement of the hypoplastic prostate glands
- seminal gland hypoplasia (MGI Ref ID J:66593)
- treatment with exogenous gonadotropins stimulated enlargement of the hypoplastic seminal vesicles
- testicular hypoplasia (MGI Ref ID J:66593)
- severe
- abnormal spermatogenesis (MGI Ref ID J:66593)
- 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
- abnormal spermatid morphology (MGI Ref ID J:66593)
- no mature spermatids are observed
- absent sexual maturation (MGI Ref ID J:66593)
- 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
- anovulation (MGI Ref ID J:66593)
- decreased male germ cell number (MGI Ref ID J:66593)
- male germ cells are significantly reduced in number
- delayed vaginal opening (MGI Ref ID J:66593)
- mutant vaginas fail to open at the normal age of puberty
- female infertility (MGI Ref ID J:66593)
- male infertility (MGI Ref ID J:66593)
- small gonad (MGI Ref ID J:66593)
- mutant gonads are severely hypoplastic
- homeostasis/metabolism phenotype
- decreased follicle stimulating hormone level (MGI Ref ID J:66593)
- 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
- decreased circulating follicle stimulating hormone level (MGI Ref ID J:66593)
- serum FSH levels are significantly reduced in both male and female mutants relative to wild-type controls
- decreased luteinizing hormone level (MGI Ref ID J:66593)
- although mutant pituitaries appear histologically intact, immunoreactive LH leves are virtually undetectable
- decreased circulating luteinizing hormone level (MGI Ref ID J:66593)
- serum LH levels are significantly reduced in male mutants relative to wild-type controls
Nr5a1tm2Klp/Nr5a1tm2Klp Tg(Cga-cre)3Sac/0
involves: 129P2/OlaHsd * C57BL/6J * SJL (conditional)
- reproductive system phenotype
- abnormal sex gland morphology (MGI Ref ID J:70412)
- Leydig cell hypoplasia (MGI Ref ID J:70412)
- 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
- absent corpus luteum (MGI Ref ID J:70412)
- absent mature ovarian follicles (MGI Ref ID J:70412)
- 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
- impaired ovarian folliculogenesis (MGI Ref ID J:70412)
- mutant mice display absence of follicular maturation beyond the antral stage
- prostate gland hypoplasia (MGI Ref ID J:70412)
- similar to that observed in mice that are heterozygous for Nr5a1tm2Klp and Nr5a1tm2.1Klp and hemizygous for Tg(Cga-cre)3Sac
- seminal gland hypoplasia (MGI Ref ID J:70412)
- similar to that observed in mice that are heterozygous for Nr5a1tm2Klp and Nr5a1tm2.1Klp and hemizygous for Tg(Cga-cre)3Sac
- small ovary (MGI Ref ID J:70412)
- 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
- decreased ovary weight (MGI Ref ID J:70412)
- 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)
- small testis (MGI Ref ID J:70412)
- 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
- decreased testis weight (MGI Ref ID J:70412)
- 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)
- absent sexual maturation (MGI Ref ID J:70412)
- both male and female mutants show little evidence for secondary sexual maturation
- female infertility (MGI Ref ID J:70412)
- male infertility (MGI Ref ID J:70412)
- small gonad (MGI Ref ID J:70412)
- 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
- small ovary (MGI Ref ID J:70412)
- 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
- decreased ovary weight (MGI Ref ID J:70412)
- 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)
- small testis (MGI Ref ID J:70412)
- 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
- decreased testis weight (MGI Ref ID J:70412)
- 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)
- uterine hypoplasia (MGI Ref ID J:70412)
- similar to that observed in mice that are heterozygous for Nr5a1tm2Klp and Nr5a1tm2.1Klp and hemizygous for Tg(Cga-cre)3Sac
- endocrine/exocrine gland phenotype
- abnormal sex gland morphology (MGI Ref ID J:70412)
- Leydig cell hypoplasia (MGI Ref ID J:70412)
- 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
- absent corpus luteum (MGI Ref ID J:70412)
- absent mature ovarian follicles (MGI Ref ID J:70412)
- 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
- impaired ovarian folliculogenesis (MGI Ref ID J:70412)
- mutant mice display absence of follicular maturation beyond the antral stage
- prostate gland hypoplasia (MGI Ref ID J:70412)
- similar to that observed in mice that are heterozygous for Nr5a1tm2Klp and Nr5a1tm2.1Klp and hemizygous for Tg(Cga-cre)3Sac
- seminal gland hypoplasia (MGI Ref ID J:70412)
- similar to that observed in mice that are heterozygous for Nr5a1tm2Klp and Nr5a1tm2.1Klp and hemizygous for Tg(Cga-cre)3Sac
- small ovary (MGI Ref ID J:70412)
- 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
- decreased ovary weight (MGI Ref ID J:70412)
- 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)
- small testis (MGI Ref ID J:70412)
- 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
- decreased testis weight (MGI Ref ID J:70412)
- 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)
- homeostasis/metabolism phenotype
- decreased circulating follicle stimulating hormone level (MGI Ref ID J:70412)
- 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)
- decreased circulating luteinizing hormone level (MGI Ref ID J:70412)
- 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
- behavior/neurological phenotype
- abnormal sexual interaction (MGI Ref ID J:70412)
- mutants do not engage in sexual activity
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:
Research Tools
Cre-lox System (loxP-flanked Sequences)
Developmental Biology Research (Cre-lox System)
Reproductive Biology Research (Cre-lox System)
| Allele Symbol | Nr5a1tm2Klp | ||
|---|---|---|---|
| Allele Name | targeted mutation 2, Keith L Parker | ||
| Allele Type | Targeted (Floxed/Frt) | ||
| Common Name(s) | F; | ||
| Mutation Made By | Linda Washburn, The Jackson Laboratory | ||
| Strain of Origin | 129P2/OlaHsd | ||
| ES Cell Line Name | E14TG2a | ||
| ES Cell Line Strain | 129P2/OlaHsd | ||
| Gene Symbol and Name | Nr5a1, nuclear receptor subfamily 5, group A, member 1 | ||
| Chromosome | 2 | ||
| Gene Common Name(s) | AD4BP; Ad4BP/SF-1; ELP; FTZ1; FTZF1; Ftz-F1; Ftzf1; SF-1; SF1; adrenal 4-binding protein; fushi tarazu 1 factor homolog, (Drosophila); steroidogenic factor 1; | ||
| Molecular Note | A single loxP site was inserted into an intron 5' to the last coding exon, and a loxP site followed by a neomycin resistance cassette was inserted 3' to this exon. This mutation flanks sequences encoding motifs essential for transcriptional activity as well as the transcription termination and polyadenyulation sequences. [MGI Ref ID J:66593] | ||
Genotyping Protocols
Nr5a1tm2Klp, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
Zhao L; Bakke M; Krimkevich Y; Cushman LJ; Parlow AF; Camper SA; Parker KL. 2001. Steroidogenic factor 1 (SF1) is essential for pituitary gonadotrope function. Development 128(2):147-54. [PubMed: 11124111] [MGI Ref ID J:66593]
Nr5a1tm2Klp relatedBakke M; Zhao L; Parker KL. 2001. Approaches to define the role of SF-1 at different levels of the hypothalamic-pituitary-steroidogenic organ axis. Mol Cell Endocrinol 179(1-2):33-7. [PubMed: 11420128] [MGI Ref ID J:125681]
Jeyasuria P; Ikeda Y; Jamin SP; Zhao L; De Rooij DG; Themmen AP; Behringer RR; Parker KL. 2004. Cell-specific knockout of steroidogenic factor 1 reveals its essential roles in gonadal function. Mol Endocrinol 18(7):1610-9. [PubMed: 15118069] [MGI Ref ID J:91352]
Kim KW; Jo YH; Zhao L; Stallings NR; Chua SC Jr; Parker KL. 2008. Steroidogenic factor 1 regulates expression of the cannabinoid receptor 1 in the ventromedial hypothalamic nucleus. Mol Endocrinol 22(8):1950-61. [PubMed: 18511494] [MGI Ref ID J:138418]
Roy A; Matzuk MM. 2006. Deconstructing mammalian reproduction: using knockouts to define fertility pathways. Reproduction 131(2):207-19. [PubMed: 16452715] [MGI Ref ID J:108425]
Wilson MJ; Jeyasuria P; Parker KL; Koopman P. 2005. The transcription factors steroidogenic factor-1 and SOX9 regulate expression of Vanin-1 during mouse testis development. J Biol Chem 280(7):5917-23. [PubMed: 15590666] [MGI Ref ID J:96928]
Zhao L; Bakke M; Hanley NA; Majdic G; Stallings NR; Jeyasuria P; Parker KL. 2004. Tissue-specific knockouts of steroidogenic factor 1. Mol Cell Endocrinol 215(1-2):89-94. [PubMed: 15026179] [MGI Ref ID J:88733]
Zhao L; Bakke M; Krimkevich Y; Cushman LJ; Parlow AF; Camper SA; Parker KL. 2001. Hypomorphic phenotype in mice with pituitary-specific knockout of steroidogenic factor 1. Genesis 30(2):65-9. [PubMed: 11416865] [MGI Ref ID J:70412]
Zhao L; Kim KW; Ikeda Y; Anderson KK; Beck L; Chase S; Tobet SA; Parker KL. 2008. Central nervous system-specific knockout of steroidogenic factor 1 results in increased anxiety-like behavior. Mol Endocrinol 22(6):1403-15. [PubMed: 18372344] [MGI Ref ID J:136159]
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, homozygous mice are bred.
| Pricing for USA, Canada and Mexico shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00
| Pricing for International shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
|
| Control | ||
|---|---|---|
| 000671 DBA/2J | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
Purchasing Information
JAX® Mice Orders
Surgical Services
Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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