B6.Cg-Dmc1^tm1Jcs/JcsJ

Stock number: 008608
Research areas: Cancer Research, Cell Biology Research, Developmental Biology Research, Endocrine Deficiency Research, Reproductive Biology Research, Research Tools

Description

These mice have a targeted "knockout" mutation of the Dmc1 gene (DMC1 dosage suppressor of mck1 homolog, meiosis-specific homologous recombination (yeast)) and may be useful in studying gametogenesis and meiosis, including double strand breaks, chromosome asynapsis, DNA repair mechanisms, homologous recombination, and the pachytene checkpoint.

Detailed 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.

Allele

Symbol: Dmc1^tm1Jcs
Name: targeted mutation 1, John C Schimenti
MGI accession ID: MGI:2176331
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Dmc1
Marker name: DNA meiotic recombinase 1
Chromosome: 15
Strain of origin: (C57BL/6 x 129S4/SvJae)F1
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.