A transgenic insertion causing cryptorchidism in mice

A distinctive feature of gonadal maturation in mammals is the movement to a n extraabdominal location. Testicular descent is a complex, multistage proc ess whereby the embryonic gonads migrate from their initial abdominal posit ion to the scrotum. Failure in this process results in cryptorchidism, a fr equent congenital birth defect in humans. We report here a new mouse transg enic insertional mutation, cryptorchidism with white spotting (crsp), Males homozygous for crsp exhibit a high intraabdominal position of the testes, associated with complete sterility, Heterozygous males have a wildtype phen otype, and homozygous females are fertile. Surgically descended testes in c rsp/crsp males show normal spermatogenesis, Using FISH and genetic analyses , the transgenic insert causing the crsp mutation has been mapped to the di stal part of mouse chromosome 5. Transgene integration resulted in a 550-kb deletion located upstream of the Brca2 gene. A candidate gene encoding a n ovel G protein-coupled receptor (Great) with an expression pattern suggesti ng involvement in testicular descent has been identified. genesis 30:26-35, 2001. (C) 2001 Wiley-Liss, Inc.