Strain Detail Sheet

Strain Name    :

129S1.129(Cg)-Nr0b1tm1.1Lja/Mmmh

Stock Number :

033003-MU

Gene Information

Gene Details [Including genotyping protocols]

(provided by MGI)
Allele Symbol: Nr0b1tm1.1Lja
Name: targeted mutation 1.1, J Larry Jameson
Alteration at locus: Knockout
Gene Symbol: Nr0b1
Name: nuclear receptor subfamily 0, group B, member 1
Chromosome: X
Alteration at locus: Knockout

Genetic Alterations:
AhCh(Dax1) was isolated from a mouse genomic DNA library, mapped and sequenced. The targeting vector contains 5.5kb of 5' and 3.1kb of 3' gene sequences. A single loxP site was inserted upstream of the splice acceptor signal of exon 2. The phosphoglycerate kinase(PGK) promotor-driven, floxed neomycon cassette was inserted downsteam of exon 2 and PGK promotor-driven thymidine kinase (TK) gene cassette was placed upstream of exon 1.

Genotype Determination:

ES Cell Line: R1

Strain Description [Including phenotype, strain background, strain development and suggested control mice]

Phenotype

Homozygous phenotype: Males: N/A; X- linked females: No disruption of sexual maturation, ovulation or fertility. Subset of follicles in ovary characterized by presence of multiple oocytes.

Heterozygous phenotype: None.


Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype

The following phenotype information may relate to one or more alleles on a genetic background differing from this MMRRC strain.
Nr0b1tm1.1Lja/Nr0b1tm1.1Lja
        involves: 129S1/Sv * 129X1/SvJ
  • reproductive system phenotype
    • polyovular ovarian follicle (MGI Ref ID J:51292)
      • subsets of follicles contain multiple oocytes
      • however, female homozygotes are fertile, produce normal litter sizes, with no apparent defects in sexual maturation, ovarian formation or ovulation
  • endocrine/exocrine gland phenotype
    • polyovular ovarian follicle (MGI Ref ID J:51292)
      • subsets of follicles contain multiple oocytes
      • however, female homozygotes are fertile, produce normal litter sizes, with no apparent defects in sexual maturation, ovarian formation or ovulation
Nr0b1tm1.1Lja/-
        involves: 129S1/Sv * 129X1/SvJ
  • reproductive system phenotype
    • abnormal spermatogenesis (MGI Ref ID J:51292)
      • spermatocytes are present at 10 weeks of age; however, germ cell depletion is observed at 14 weeks of age, indicating a defect in the maintenance of spermatogenesis
    • abnormal testis morphology (MGI Ref ID J:51292)
      • male hemizygotes display progressive loss of the germinal epithelium during postnatal testicular maturation
      • abnormal Leydig cell morphology (MGI Ref IDs J:81356, J:71710)
        • at 12 weeks, Leydig cells in the interstitial space near the rete appear hyperplastic, with large mitochondria containing numerous tubular cristae (MGI Ref ID J:71710)
        • in contrast, Leydig cells found in the seminiferous tubules are smaller and contain smaller mitochondria (MGI Ref ID J:71710)
        • neither type of Leydig cell displays the cytoplasmic swirls of saccular endoplasmic reticulum typical of adult wild-type Leydig cells (MGI Ref ID J:71710)
        • fetal Leydig cell development is arrested, with Leydig cells restricted to the ventral surface of the gonad (MGI Ref ID J:81356)
        • Leydig cell hyperplasia (MGI Ref IDs J:51292, J:71710)
          • at 10 weeks, interstitial Leydig cells show cellular hypertrophy and hyperplasia in the vicinity of severely degenerated seminiferous tubules (MGI Ref ID J:51292)
          • at >1 yr of age, most male hemizygotes exhibit Leydig cell hyperplasia (MGI Ref ID J:71710)
          • a few cases of Leydig cell neoplasia are also observed (MGI Ref ID J:71710)
        • ectopic Leydig cells (MGI Ref IDs J:81356, J:71710)
          • at 12 weeks of age, seminiferous tubules close to the rete testis exhibit ectopic Leydig cells, distinct from the hyperplastic Leydig cells found in the interstitial space (MGI Ref ID J:71710)
          • at 13.5 dpc, Leydig cells, which normally reside in the peritubular space and extend from the coelomic surface to the dorsal surface of the gonad, are restricted to the coelomic surface and almost completely excluded from the dorsal part of the gonad (MGI Ref ID J:81356)
      • abnormal Sertoli cell development (MGI Ref ID J:81356)
        • at 13.5 dpc, organization and differentiation of mutant Sertoli cells is decreased relative to wild-type
        • Sertoli cell hyperplasia (MGI Ref ID J:71710)
          • at 12 weeks of age, abnormal proliferation of Sertoli cells results in the blockage of the rete testis and efferent ducts, impeding the passage of sperm into the epididymis
      • abnormal efferent ductules of testis morphology (MGI Ref ID J:71710)
        • at 12 weeks of age, the proximal and middle efferent ductules are obstructed by Sertoli cells, blocking the passage of sperm, and the epithelium of the efferent duct is frequently overgrown
        • notably, the epithelia display numerous basally positioned lipid deposits not observed in wild-type
        • in contrast, the mutant epididymides appear morphologically normal
      • abnormal peritubular myoid cell morphology (MGI Ref ID J:71710)
        • at 12 weeks of age, peritubular myoid cells appear poorly differentiated
        • no basement membrane between the myoid cells and Sertoli cells is observed
        • decreased number of peritubular myoid cells (MGI Ref ID J:81356)
          • at 13.5 dpc, the number of peritubular myoid cells, which normally surround the testis cords, is reduced
          • BrdU labeling of peritubular myoid cells is low, consistent with decreased proliferation
      • abnormal seminiferous epithelium morphology (MGI Ref ID J:71710)
        • at 12 weeks of age, vacuolation of the seminiferous epithelium and lipid accumulation are common in affected tubules, especially near the rete and in all tubules in older males, indicating a breakdown in Sertoli-germ cell junctions
      • abnormal seminiferous epithelium morphology (MGI Ref ID J:51292)
        • at 10 weeks of age, some tubules display thin, irregular epithelia with sloughing of germ cells into the lumen
        • occasional tubules show active spermatogenesis with stratified germinal epithelium and a relatively normal appearance
      • abnormal testis cord formation (MGI Ref ID J:81356)
        • at 13.5 dpc, testis cord formation is delayed, as shown by a decreased number of cords that are poorly distinguished from the peritubular space
        • at 13.5 dpc, the coelomic vessel is still present on the ventral surface; however, the ventral-dorsal width is intermediate between male and female gonads
        • at 13.5 dpc, germ cells and Sertoli cells cluster together within the dorsal surface of the gonad, but only a few PTM cells are observed
        • the basal lamina which defines the edges of individual testis cords is either disrupted or absent at 12.5, 13.5 and 14.5 dpc
        • at 14.5 dpc, tes tis cord-like structures are present but appear smaller, irregular in shape, and with frequent breaks in laminin localization
        • disorganized testis cords (MGI Ref ID J:81356)
          • at 13.5 dpc, testis cords appear disorganized and incompletely formed; however, the number of germ and Sertoli cells and the expression of Sertoli-specific markers appear to be normal
          • at 14.5 dpc, testis cords remain rudimentary, with occasional scattered PTM cells present at the ventral surface, leaving the dorsal half of the gonad more disorganized
          • by 17.5 dpc, testis cords are larger than normal and more pleomorphic in shape, without clearly defined borders
      • dilated seminiferous tubules (MGI Ref ID J:71710)
        • adult male hemizygotes exhibit dilated seminiferous tubules at all test ages
        • tubule dilation is transient, with marked variability in the proportions of normal, dilated, and degenerating seminiferous tubules between different males of different ages
      • ectopic Sertoli cells (MGI Ref ID J:71710)
        • at 12 weeks of age, the rete testis is blocked by ectopic Sertoli cells found within the lumen of the seminiferous tubules and efferent ducts
      • rete testis obstruction (MGI Ref ID J:71710)
        • at 12 weeks of age, the rete testis is blocked by abnormally located Sertoli cells, creating a tailback of necrosing sperm in the testis
      • seminiferous tubule degeneration (MGI Ref IDs J:51292, J:71710)
        • epithelial dysgenesis and degeneration exhibited at 10 weeks of age (MGI Ref ID J:51292)
        • adult male hemizygotes exhibit degenerating seminiferous tubules at all test ages (MGI Ref ID J:71710)
      • small testis (MGI Ref ID J:51292)
        • male hemizygotes have small testes despite normal serum levels of testosterone and gonadotropins
        • decreased testis weight (MGI Ref IDs J:51292, J:71710)
          • approximately 50% reduction in weight relative to wild-type (MGI Ref ID J:51292)
          • at 12 weeks of age, mutant testes weigh significantly less than wild-type (126.2

            Strain of Origin: 129, B6 mix

            Strain genetic background: 129S1/SvImJ

            Strain Development: The strain was developed by insertion of a targeted mutation into ES cells which were then injected to make chimeras.Chimeras were backcrossed to 129Sv/J(now 129X1/J)to generate targeted founder animals in 1998.Deleted animals were created by mating CMVCre animals and are currently maintained as KOs w/o Cre. From 1998- 2001 the strain was intercrossed and backcrossed to 129S1SvIMJ. In 2005 the strain was submitted for speed congenics with Charles River and is now congenic on 129S1SvIMJ.

            Suggested Control Mice:

            • Wildtype littermates

Research Applications

  • Developmental Biology
  • Endocrine Deficiency
  • Models for Human Disease
  • Reproduction

Strain Origin

Donor: J. Larry Jameson, MD. PhD, Northwestern University

Primary Reference:

  • Yu RN; Ito M; Saunders TL; Camper SA; Jameson JL, Role of Ahch in gonadal development and gametogenesis [see comments], Nat Genet 1998 Dec;20(4):353-7. (Medline PMID: 9843206)
  • Jeffs B; Meeks JJ; Ito M; Martinson FA; Matzuk MM; Jameson JL; Russell LD, Blockage of the rete testis and efferent ductules by ectopic sertoli and leydig cells causes infertility in dax1-deficient male mice., Endocrinology 2001 Oct;142(10):4486-95. (Medline PMID: 11564714)
  • Jeffs B; Ito M; Yu RN; Martinson FA; Wang ZJ; Doglio LT; Jameson JL, Sertoli cell-specific rescue of fertility, but not testicular pathology, in Dax1 (Ahch)-deficient male mice., Endocrinology 2001 Jun;142(6):2481-8. (Medline PMID: 11356697)

Colony and Husbandry Information

Special Considerations

Backcross to 129S1/SvImJ.

Health Status Report

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc@missouri.edu.

Order Request Information

Availability Level

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Conditions of Distribution [Including applicable technology transfer agreements]

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

The donor or their institution limits the distribution to non-profit institutions only.

Fees

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # - Description Distribution
Fee/unit (US $)
Units Notes
033003-MU-RESUSLitter recovered from cryo-archive
$2,022.00
Non-Profit
Litter Recovered litter1; additional fees for any special requests.
033003-MU-SPERMCryo-preserved spermatozoa
$437.00
Non-Profit
Aliquot Approximate quantity.2

1 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

3 An aliquot contains a sufficient number of embryos (in one or more vials and based on the transfer success rate of the MMRRC facility) to transfer to at least two recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section above). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.



To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.



The MMRRC is a collaborative effort, funded by grants from DPCPSI of the NIH.

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