B6N.129P2-Dazl^tm1Hjc/J

Stock number: 023802
Research areas: Cell Biology Research, Reproductive Biology Research

Description

These mice carry a targeted knockout of Dazl (deleted in azoospermia-like) on the C57BL/6N genetic background. Homozygotes are infertile, but otherwise healthy. Germ cells fail to activate genes required for both male-specific and female-specific sexual differentiation in homozygous knockout mice. This phenotype appears to be sensitive to the genetic background.

Detailed description

Dazl (deleted in azoospermia-like) is a germ cell-specific RNA binding protein that is expressed in post-migratory primordial germ cells as well as postnatal germ cells. On the C57BL/6N genetic background, it acts as a competence factor for gametogenesis.

These mice carry a targeted knockout of Dazl on the C57BL/6N genetic background. RT-PCR confirms the absence of transcript and western blot/immunohistochemistry fail to detect any protein generated from the null allele. Heterozygotes are viable and fertile. Homozygotes are infertile, but otherwise healthy. Germ cells fail to activate genes required for both male-specific and female-specific sexual differentiation in homozygous knockout mice. Post migratory germ cells retain PGC-like gene expression and eventually die. This phenotype appears to be sensitive to strain background, however.

Development

Exons 6 and 7, and all but five amino acids of exon 5 were replaced by a neomycin resistance cassette via homologous recombination in 129P2/OlaHsd-derived CGR8 embryonic stem (ES) cells. This strain was originally maintained on an outbred MF1 genetic background in Howard Cooke's laboratory, but has since been backcrossed to C57BL/6NTac by the donating laboratory for more than 27 generations. Upon arrival at The Jackson Laboratory, this line was re-derived with C57BL/6NJ (see Stock No. 005304). All Y chromosomes and mitochondria are of C57BL/6 origin.

Allele

Symbol: Dazl^tm1Hjc
Name: targeted mutation 1, Howard J Cooke
MGI accession ID: MGI:2181904
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Dazl
Marker name: deleted in azoospermia-like
Chromosome: 17
Strain of origin: 129P2/OlaHsd
Molecular note: Exons 5 through 7 were disrupted by the insertion of a neomycin selection cassette. Mutant transcripts were undetected via RT-PCR analysis of total RNA isolated from heterozygous mice. Western blot analysis of testis extracts showed an absence of protein in homozygous mutant mice.