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

Type Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation ?pN1 Generation Definitions   Donating Investigator John Schimenti,   Cornell University

Description
While mice heterozygous for this meiosis-specific RecA homolog (Dmc1) mutation are viable and fertile, homozygotes are viable but sterile due to arrest of gametogenesis in the first meiotic prophase (prophase I). No RNA message from the targeted gene is observed in homozygous testis. Homozygous males have reduced testis size and no mature spermatozoa in the epididymis; spermatocytes undergo meiotic arrest from defective double strand break repair and extensive chromosome asynapsis. Homozygous females exhibit defective oogenesis due to similar aberrations occurring at the pachytene stage or earlier and thus have small, malformed ovaries with complete depletion of oocytes and follicles by adulthood. These Dmc1-mutant mice may be useful in studying gametogenesis and meiosis (including double strand breaks, chromosome asynapsis, DNA repair mechanisms, homologous recombination, and the pachytene checkpoint).

Development
A targeting vector was designed to replace a region of the targeted gene containing the RecA-like DNA binding motif (GEFRTGKT) with a neomycin resistance cassette. This construct was electroporated into (C57BL/6 x 129S4Sv/Jae)F1-derived V6.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric males were bred with C57BL/6J females. Mutant mice were backcrossed to C57BL/6J for at least 10 generations prior to arrival at The Jackson Laboratory. Upon arrival, mutant mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

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

Dmc1^tm1Jcs/Dmc1^tm1Jcs

        involves: 129S4/SvJae * C57BL/6J

• reproductive system phenotype
• abnormal reproductive system morphology   (MGI Ref ID J:47308)
• • abnormal gametogenesis   (MGI Ref ID J:47308)
  • • abnormal oogenesis   (MGI Ref ID J:47308)
    • • abnormal female meiosis
        • defects during prophase of meiosis I beginning at, or prior to, the pachytene stage   (MGI Ref ID J:47308)
      • absent oocytes   (MGI Ref ID J:47308)
    • abnormal spermatogenesis   (MGI Ref ID J:47308)
    • • arrest of male meiosis
        • arrest during prophase of meiosis I at a zygotene-like stage in which chromosomal synapsis was not initiated   (MGI Ref ID J:47308)
      • azoospermia   (MGI Ref ID J:47308)
  • absent ovarian follicles   (MGI Ref ID J:47308)
  • decreased ovary weight
    • approximately one-third the weight of those of controls   (MGI Ref ID J:47308)
  • decreased testis weight
    • approximately one-third the weight of those of controls   (MGI Ref ID J:47308)
• infertility   (MGI Ref ID J:47308)
• • female infertility   (MGI Ref ID J:47308)
  • male infertility   (MGI Ref ID J:47308)
• endocrine/exocrine gland phenotype
• absent ovarian follicles   (MGI Ref ID J:47308)
• decreased ovary weight
  • approximately one-third the weight of those of controls   (MGI Ref ID J:47308)
• decreased testis weight
  • approximately one-third the weight of those of controls   (MGI Ref ID J:47308)

View Research Applications

Research Applications

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

Cancer Research
Other
      DNA Repair

Cell Biology Research
DNA Damage Response

Developmental Biology Research
Internal/Organ Defects
      gonads

Endocrine Deficiency Research
Gonad Defects

Reproductive Biology Research
Developmental Defects Affecting Gonads
      germ cell deficient
Endocrine Deficiencies Affecting Gonads
Fertility Defects

Research Tools
Reproductive Biology Research
      male germ cells
      oocyte

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Dmc1tm1Jcs
Allele Name		targeted mutation 1, John C Schimenti
Allele Type		Targeted (knock-out)
Common Name(s)		Dmc1-;
Mutation Made By		John Schimenti,   Cornell University
Strain of Origin		(C57BL/6 x 129S4/SvJae)F1
ES Cell Line Name		v6.5
ES Cell Line Strain		(C57BL/6 x 129S4/SvJae)F1
Gene Symbol and Name		Dmc1, DMC1 dosage suppressor of mck1 homolog, meiosis-specific homologous recombination (yeast)
Chromosome		15
Gene Common Name(s)		DMC1H; Dmc1h; HsLim15; LIM15; Mei11; dJ199H16.1; disrupted meiotic cDNA homolog 1; meiosis defective 11; sgdp; spermatogonial depletion;
Molecular Note		A neomycin selection cassette replaced a genomic fragment containing sequences encoding the conserved DNA binding motif required for protein activity. RT-PCR analysis on RNA derived from testis of homozygous males demonstrated that no detectable transcript was produced from this allele. [MGI Ref ID J:47308]

Genotyping

Genotyping Information

Genotyping Protocols

Dmc1^tm1Jcs, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Pittman DL; Cobb J; Schimenti KJ; Wilson LA; Cooper DM; Brignull E ; Handel MA ; Schimenti JC. 1998. Meiotic prophase arrest with failure of chromosome synapsis in mice deficient for Dmc1, a germline-specific RecA homolog. Mol Cell 1(5):697-705. [PubMed: 9660953]  [MGI Ref ID J:47308]

Additional References

Dmc1^tm1Jcs related

Bannister LA; Pezza RJ; Donaldson JR; de Rooij DG; Schimenti KJ; Camerini-Otero RD; Schimenti JC. 2007. A dominant, recombination-defective allele of Dmc1 causing male-specific sterility. PLoS Biol 5(5):e105. [PubMed: 17425408]  [MGI Ref ID J:122037]

Barchi M; Mahadevaiah S; Di Giacomo M; Baudat F; de Rooij DG; Burgoyne PS; Jasin M; Keeney S. 2005. Surveillance of different recombination defects in mouse spermatocytes yields distinct responses despite elimination at an identical developmental stage. Mol Cell Biol 25(16):7203-15. [PubMed: 16055729]  [MGI Ref ID J:133053]

Daniel K; Lange J; Hached K; Fu J; Anastassiadis K; Roig I; Cooke HJ; Stewart AF; Wassmann K; Jasin M; Keeney S; Toth A. 2011. Meiotic homologue alignment and its quality surveillance are controlled by mouse HORMAD1. Nat Cell Biol 13(5):599-610. [PubMed: 21478856]  [MGI Ref ID J:173089]

Di Giacomo M; Barchi M; Baudat F; Edelmann W; Keeney S; Jasin M. 2005. Distinct DNA-damage-dependent and -independent responses drive the loss of oocytes in recombination-defective mouse mutants. Proc Natl Acad Sci U S A 102(3):737-42. [PubMed: 15640358]  [MGI Ref ID J:96250]

Lange J; Pan J; Cole F; Thelen MP; Jasin M; Keeney S. 2011. ATM controls meiotic double-strand-break formation. Nature 479(7372):237-40. [PubMed: 22002603]  [MGI Ref ID J:178306]

Li X; Schimenti JC. 2007. Mouse Pachytene Checkpoint 2 (Trip13) Is Required for Completing Meiotic Recombination but Not Synapsis. PLoS Genet 3(8):e130. [PubMed: 17696610]  [MGI Ref ID J:123677]

Liebe B; Petukhova G; Barchi M; Bellani M; Braselmann H; Nakano T; Pandita TK; Jasin M; Fornace A; Meistrich ML; Baarends WM; Schimenti J; de Lange T; Keeney S; Camerini-Otero RD; Scherthan H. 2006. Mutations that affect meiosis in male mice influence the dynamics of the mid-preleptotene and bouquet stages. Exp Cell Res 312(19):3768-81. [PubMed: 17010969]  [MGI Ref ID J:147391]

Mahadevaiah SK; Bourc'his D; de Rooij DG; Bestor TH; Turner JM; Burgoyne PS. 2008. Extensive meiotic asynapsis in mice antagonises meiotic silencing of unsynapsed chromatin and consequently disrupts meiotic sex chromosome inactivation. J Cell Biol 182(2):263-76. [PubMed: 18663141]  [MGI Ref ID J:139518]

Reinholdt LG; Schimenti JC. 2005. Mei1 is epistatic to Dmc1 during mouse meiosis. Chromosoma 114(2):127-34. [PubMed: 15928951]  [MGI Ref ID J:103876]

Health & husbandry

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.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, heterozygous mice may be bred together (or to wildtype siblings or C57BL/6J inbred mice). Homozygous mice are viable but sterile.

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

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

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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