129S1/SvImJ-Ar^tm2.1Reb/J

Stock number: 018451
Research areas: Developmental Biology Research, Reproductive Biology Research, Research Tools

Description

Exon 1 of the X-linked androgen receptor (Ar) gene is floxed, making this conditional mutant strain useful when studying male sexual development and fertility.

Detailed description

These mice possess loxP sites flanking exon 1 of the X-linked androgen receptor (Ar) gene. AR is a nuclear transcription factor expressed in Sertoli cells which becomes activated by binding to testosterone or dihydrotestosterone. AR is required for male embryonic sexual differentiation, the development of male sexual characteristics, and the regulation of spermatogenesis. Homozygous females and hemizygous males are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon 1 deleted in cre-expressing tissues, abolishing gene function.

For example, breeding these mice to 129S.FVB-Tg(Amh-cre)8815Reb/J mice (Stock No. 007915), results in the production of a new variety of Sertoli cell AR knock out (SCARKO) mice. These mice are azoospermic and show a block in meiosis in Sertoli cells, with normal expression of Ar in Leydig cells and myoid epithelial cells.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector was designed to insert a single loxP site upstream of exon 1, and a frt-flanked neomycin resistance (neo) cassette followed by another loxP site downstream of exon 1 of the androgen receptor (Ar) gene. The construct was electroporated into 129S1/SvImJ-derived embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a CMV-Flp expression plasmid to delete the neo cassette. Correctly targeted ES cells, lacking neo, were injected into C57BL/6J blastocysts and resulting chimeric males were bred with 129S1/SvImJ females (Stock No. 002448) to establish a colony. Upon arrival, mice were bred to 129S1/SvImJ inbred mice for at least one generation.

Allele

Symbol: Ar^tm2.1Reb
Name: targeted mutation 2.1, Robert E Braun
MGI accession ID: MGI:5431884
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Ar
Marker name: androgen receptor
Chromosome: X
Strain of origin: 129S1/SvImJ
Molecular note: A targeting vector was designed to insert a single loxP site upstream of exon 1 and the Ar start site, and a frt-flanked neomycin resistance (neo) cassette, followed by another loxP site, downstream of exon 1. Flp-mediated recombination removed the neo cassette.