Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names B6;129S7-Amhtm1Bhr    (Changed: 15-DEC-04 ) Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation F?+3N1p Generation Definitions   Donating Investigator Dr. Richard Behringer,   Univ of Texas, MD Anderson Cancer Center

Description
Male mice homozygous for the Amh^tm1Bhr mutation have testes that are fully descended and produce functional sperm. They also develop a uterus which interferes with sperm transfer rendering most infertile. The testes develop Leydig cell hyperplasia.

Development
The Amh^tm1Bhr mutant strain was developed in the laboratory of Dr. Richard Behringer at the University of Texas, MD Anderson Cancer Center. The 129-derived AB-1 ES cell line was used.

Control Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying   Amh^tm1Bhr allele

002188

B6.129S7-Amhtm1Bhr/J

View Strains carrying   Amh^tm1Bhr     (1 strain)

Strains carrying other alleles of Amh

007915

129S.FVB-Tg(Amh-cre)8815Reb/J

View Strains carrying other alleles of Amh     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Persistent Mullerian Duct Syndrome, Types I and II; PMDS   (AMH)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Amh^tm1Bhr/Amh^tm1Bhr

        either: (involves 129P3/J * 129S7/SvEvBrd) or (involves: 129S7/SvEvBrd * C57BL/6)

• endocrine/exocrine gland phenotype
• Leydig cell hyperplasia
  • focal hyperplasia in 27% of males 10 weeks or older   (MGI Ref ID J:21396)
  • in spite of the hyperplasia, the cells were functionally normal   (MGI Ref ID J:21396)
  • one neoplasm containing multiple foci of leydig cell hyperplasia was detected   (MGI Ref ID J:21396)
• reproductive system phenotype
• *normal* reproductive system phenotype
  • XX females were fertile and displayed normal uteri containing morphologically normal oviducts   (MGI Ref ID J:21396)
• • Leydig cell hyperplasia
    • focal hyperplasia in 27% of males 10 weeks or older   (MGI Ref ID J:21396)
    • in spite of the hyperplasia, the cells were functionally normal   (MGI Ref ID J:21396)
    • one neoplasm containing multiple foci of leydig cell hyperplasia was detected   (MGI Ref ID J:21396)
  • male pseudohermaphroditism
    • XY male mice developed hypoplastic female structures derived from the Mullerian duct, namely a uterus, uncoiled oviducts, and a vagina   (MGI Ref ID J:21396)
    • uterine horns paralleled the vas deferens and joined to form cervix that opened into a vagina   (MGI Ref ID J:21396)
    • the physical association of the uterine horns with the vas deferens caused the horns to be pulled caudally   (MGI Ref ID J:21396)
    • XY males displayed normal sized testes that were fully descended and spermatogenesis was unimpaired   (MGI Ref ID J:21396)
    • proper differentiation of the Wolffian duct system   (MGI Ref ID J:21396)
  • reduced male fertility
    • 13% of males were able to impregnate wild-type females   (MGI Ref ID J:21396)
    • infertility putatively due to a blockage of sperm movement resulting in a diversion from the normal pathway   (MGI Ref ID J:21396)
  • secondary sex reversal   (MGI Ref ID J:21396)

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Amh^tm1Bhr/Amh⁺

        involves: 129S7/SvEvBrd * C57BL/6

• endocrine/exocrine gland phenotype
• increased ovary weight
  • the ovarian weight was greater than that of wild-type mice and less than that of homozygous mutant mice   (MGI Ref ID J:58577)
• reproductive system phenotype
• increased ovary weight
  • the ovarian weight was greater than that of wild-type mice and less than that of homozygous mutant mice   (MGI Ref ID J:58577)

Amh^tm1Bhr/Amh^tm1Bhr

        involves: 129S7/SvEvBrd * C57BL/6

• endocrine/exocrine gland phenotype
• increased follicle recruitment
  • increased numbers of preantral and small antral follicles at 25 days and 4 months   (MGI Ref ID J:58577)
  • reduced number of primordial follicles observed at 4 months, with further decrease at 13   (MGI Ref ID J:58577)
• increased ovary weight
  • while the ovaries were morphologically normal at 25 days and 13 months, the weight was 1.8 fold higher than wild-type at 4 months of age   (MGI Ref ID J:58577)
• homeostasis/metabolism phenotype
• suppressed circulating follicle stimulating hormone level
  • observed in females 4 months of age   (MGI Ref ID J:58577)
• reproductive system phenotype
• increased follicle recruitment
  • increased numbers of preantral and small antral follicles at 25 days and 4 months   (MGI Ref ID J:58577)
  • reduced number of primordial follicles observed at 4 months, with further decrease at 13   (MGI Ref ID J:58577)
• increased ovary weight
  • while the ovaries were morphologically normal at 25 days and 13 months, the weight was 1.8 fold higher than wild-type at 4 months of age   (MGI Ref ID J:58577)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Amh^tm1Bhr related

Cancer Research
Increased Tumor Incidence
      Gonadal Tumors
      Gonadal Tumors: Leydig cell tumors

Developmental Biology Research
Internal/Organ Defects
      gonads

Endocrine Deficiency Research
Gonad Defects

Reproductive Biology Research
Developmental Defects Affecting Gonads
Endocrine Deficiencies Affecting Gonads
Fertility Defects
Gonadal Tumors
      Leydig cell hyperplasia

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Amhtm1Bhr
Allele Name		targeted mutation 1, Richard R Behringer
Allele Type		Targeted (knock-out)
Common Name(s)		AMH(-); AMHKO; MIS-KO; delta1 (null);
Mutation Made By		Dr. Richard Behringer,   Univ of Texas, MD Anderson Cancer Center
Strain of Origin		129S7/SvEvBrd-Hprt<+>
ES Cell Line Name		AB1
ES Cell Line Strain		129S7/SvEvBrd-Hprt<+>
Gene Symbol and Name		Amh, anti-Mullerian hormone
Chromosome		10
Gene Common Name(s)		MIF; MIS; Mullerian inhibiting substance;
Molecular Note		A 0.6 kb genomic fragment containing part of exon 1 and exon 2 was replaced with a neomycin selection cassette. [MGI Ref ID J:21396]

Genotyping

Genotyping Information

Genotyping Protocols

Amh^tm1Bhr, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Behringer RR; Finegold MJ; Cate RL. 1994. Mullerian-inhibiting substance function during mammalian sexual development. Cell 79(3):415-25. [PubMed: 7954809]  [MGI Ref ID J:21396]

Additional References

Racine C; Rey R; Forest MG; Louis F; Ferre A; Huhtaniemi I; Josso N; di Clemente N. 1998. Receptors for anti-mullerian hormone on Leydig cells are responsible for its effects on steroidogenesis and cell differentiation. Proc Natl Acad Sci U S A 95(2):594-9. [PubMed: 9435237]  [MGI Ref ID J:45585]

Amh^tm1Bhr related

Allard S; Adin P; Gouedard L; di Clemente N; Josso N; Orgebin-Crist MC; Picard JY; Xavier F. 2000. Molecular mechanisms of hormone-mediated Mullerian duct regression: involvement of beta-catenin. Development 127(15):3349-60. [PubMed: 10887090]  [MGI Ref ID J:62986]

Arango NA; Lovell-Badge R; Behringer RR. 1999. Targeted mutagenesis of the endogenous mouse Mis gene promoter: in vivo definition of genetic pathways of vertebrate sexual development. Cell 99(4):409-19. [PubMed: 10571183]  [MGI Ref ID J:58474]

Durlinger AL; Kramer P; Karels B; de Jong FH; Uilenbroek JT; Grootegoed JA; Themmen AP. 1999. Control of primordial follicle recruitment by anti-Mullerian hormone in the mouse ovary. Endocrinology 140(12):5789-96. [PubMed: 10579345]  [MGI Ref ID J:58577]

Jeske YW; Mishina Y; Cohen DR; Behringer RR; Koopman P. 1996. Analysis of the role of Amh and Fra1 in the Sry regulatory pathway. Mol Reprod Dev 44(2):153-8. [PubMed: 9115712]  [MGI Ref ID J:33399]

Kobayashi A; Shawlot W; Kania A; Behringer RR. 2004. Requirement of Lim1 for female reproductive tract development. Development 131(3):539-49. [PubMed: 14695376]  [MGI Ref ID J:133086]

Mishina Y; Rey R; Finegold MJ; Matzuk MM; Josso N; Cate RL; Behringer RR. 1996. Genetic analysis of the Mullerian-inhibiting substance signal transduction pathway in mammalian sexual differentiation. Genes Dev 10(20):2577-87. [PubMed: 8895659]  [MGI Ref ID J:36027]

Roberts LM; Visser JA; Ingraham HA. 2002. Involvement of a matrix metalloproteinase in MIS-induced cell death during urogenital development. Development 129(6):1487-96. [PubMed: 11880357]  [MGI Ref ID J:74911]

Ross AJ; Tilman C; Yao H; MacLaughlin D; Capel B. 2003. AMH induces mesonephric cell migration in XX gonads. Mol Cell Endocrinol 211(1-2):1-7. [PubMed: 14656469]  [MGI Ref ID J:125579]

Visser JA; Durlinger AL; Peters IJ; van den Heuvel ER; Rose UM; Kramer P; de Jong FH; Themmen AP. 2007. Increased oocyte degeneration and follicular atresia during the estrous cycle in anti-Mullerian hormone null mice. Endocrinology 148(5):2301-8. [PubMed: 17255205]  [MGI Ref ID J:129610]

Wang PY; Protheroe A; Clarkson AN; Imhoff F; Koishi K; McLennan IS. 2009. Mullerian inhibiting substance contributes to sex-linked biases in the brain and behavior. Proc Natl Acad Sci U S A 106(17):7203-8. [PubMed: 19359476]  [MGI Ref ID J:148337]

Wu X; Arumugam R; Baker SP; Lee MM. 2005. Pubertal and adult Leydig cell function in Mullerian inhibiting substance-deficient mice. Endocrinology 146(2):589-95. [PubMed: 15514087]  [MGI Ref ID J:105534]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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.

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