Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain C57BL/6 Donor Strain 129S7 via AB1 ES cell line (+Hprt-bm2) Generation N5+1+F1   Donating Investigator The Jackson Laboratory,

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. Homozygous females are fertile.

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. The C57BL/6J strain was generated by backcrossing mice carrying the Amh^tm1Bhr mutation 5 or more times to C57BL/6J inbred mice.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Amh^tm1Bhr allele

002187

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)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

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.

Amh^tm1Bhr/Amh⁺

        involves: 129S7/SvEvBrd * C57BL/6

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

Amh^tm1Bhr/Amh^tm1Bhr

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

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

Amh^tm1Bhr/Amh^tm1Bhr

        involves: 129S7/SvEvBrd * C57BL/6

• endocrine/exocrine gland phenotype
• increased follicle recruitment (MGI Ref ID J:58577)
  • increased numbers of preantral and small antral follicles at 25 days and 4 months
  • reduced number of primordial follicles observed at 4 months, with further decrease at 13
• increased ovary weight (MGI Ref ID J:58577)
  • 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
• homeostasis/metabolism phenotype
• suppressed circulating follicle stimulating hormone level (MGI Ref ID J:58577)
  • observed in females 4 months of age
• reproductive system phenotype
• increased follicle recruitment (MGI Ref ID J:58577)
  • increased numbers of preantral and small antral follicles at 25 days and 4 months
  • reduced number of primordial follicles observed at 4 months, with further decrease at 13
• increased ovary weight (MGI Ref ID J:58577)
  • 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

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: 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

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		Richard Behringer,   Univ of Texas, MD Anderson Cancer Center
Strain of Origin		129S7/SvEvBrd-Hprt1<+>
ES Cell Line Name		AB1
ES Cell Line Strain		129S7/SvEvBrd-Hprt1<+>
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, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

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

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]

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

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-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
	000664 C57BL/6J
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.

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Ordering and Purchasing Information

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

Contact information

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

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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