Strain Name:

D2.129P2(B6)-Nr5a1tm2Klp/EiJ

Stock Number:

007042

Availability:

Repository-Cryopreserved

Use Restrictions Apply, see Terms of Use

Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered Mutant Mice.
Specieslaboratory mouse
Donor Strain 129P2/OlaHsd via E14TG2a ES cell line
GenerationN9F2pN1
 
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 Information

  Control
   000671 DBA/2J
 
  Considerations for Choosing Controls

Related Strains

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)

Additional Web Information

Cre-lox Systems

Phenotype

Phenotype Information

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
    • ovary hypoplasia (MGI Ref ID J:66593)
      • severe
    • testicular hypoplasia (MGI Ref ID J:66593)
      • severe
  • 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)

Genes & Alleles

Gene & Allele Information

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 Origin129P2/OlaHsd
ES Cell Line NameE14TG2a
ES Cell Line Strain129P2/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

Genotyping Information

Genotyping Protocols

Nr5a1tm2Klp, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

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]

Additional References

Nr5a1tm2Klp related

Bakke 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]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, homozygous mice are bred.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Pricing for USA, Canada and Mexico shipping destinations View International pricing
Weeks of AgePrice*Gender
Cryorecovery Fee $1900.00
*Price(s) in US dollars ($)

Additional Supply Details

Pricing for International shipping destinations View USA Canada and Mexico pricing
Weeks of AgePrice*Gender
Cryorecovery Fee $2470.00
*Price(s) in US dollars ($)

Additional Supply Details

Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes
  • Cryorecovery - Standard.
    The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
    One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845.

  • This strain is included in the Induced Mutant Resource Colony collection.

Control Information

  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.

General Terms and Conditions


See Terms of Use


The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use


General Terms and Conditions


Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

Contact information

General inquiries

Contracts Administration

phone:207-288-6470
fax:207-288-6655

JAX® Mice & Services Conditions of Use

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