Midgestation lethality in mice deficient for the RecA-related gene, Rad51d/Rad51l3

Homologous recombination (HR) occurs in all organisms, and is important for repair of DNA damage, chromosome segregation during meiosis, and genetic d iversification. Genes critical for recombinational DNA repair and meiotic r ecombination include members of the RecA/RAD51 family, of which seven have been identified in mammals. Here, we describe the disruption of Rad51d (rec ently designated Rad51I3) in mice and its phenotypic consequences. Rad51d-d eficient mice die between 8.5 and 11.5 dpc, The affected embryos are smalle r than littermates, posteriorly truncated, and developmentally delayed. Emb ryonic fibroblasts from mutant embryos could not be propagated more than on e generation in culture. Rad51d-deficient blastocysts were not sensitive to gamma radiation or methylmethanesulfonate (MMS) in blastocyst outgrowth ex periments. The variable and generalized developmental progression defects i n Rad51d-deficient embryos suggests that mutant cells may undergo delayed o r suboptimal repair of DNA damage, resulting in accumulated degrees of muta tion and/or cell cycle perturbation that are incompatible with normal embry onic development. genesis 26:167-173, 2000, (C) 2000 Wiley-Liss, Inc.