The mouse gcd2 mutation causes primordial germ cell depletion

Germ cell depletion 2 (gcd2) is a chemically induced recessive mutation that causes infertility in male and female mice. The infertility is caused by germ cell depletion as early as 11.5 days post-coitum, when primordial germ cells have completed their migration to the embryonic gonads. Thus, the gcd2 mutation affects the proliferation and/or survival of germ cells after they arrive in the embryonic gonad, a developmental time when little is known about the requirements for germ cell proliferation and survival. The sterility phenotype is incompletely penetrant, has variable expressivity, and is modulated by strain background. The penetrance ranges from 37% in strain C57BL/6J to nearly 100% in CAST/EiJ. Genetic mapping localized gcd2 to a approximately 1Mb region on Chr 2. This interval contains a small number of annotated genes, of which none are known to have a role in germ cell development. Sequencing the coding regions of these genes failed to reveal a mutation, and BACs containing two of the candidate genes failed to rescue the phenotype. This raises the possibilities that the gcd2 mutation resides in non-coding sequences, and regulates genes outside the genetically defined critical region.