Targeted disruption of the Rad51 gene leads to lethality in embryonic mice.

TLDR

The mouse Rad51 gene, homologous to bacterial recA and yeast RAD51, is essential for homologous recombination and DNA repair. The study aimed to determine RAD51’s physiological role by targeting its gene in embryonic stem cells. Heterozygous Rad51‑null mice were intercrossed and offspring genotyped to assess viability. Homozygous Rad51‑null embryos were lethal before birth, with no surviving pups and no viable double‑knockout ES cells, indicating RAD51 is essential for cell proliferation and that its loss causes cell‑autonomous pre‑implantation lethality.

Abstract

The mouse Rad51 gene is a mammalian homologue of the Escherichia coli recA and yeast RAD51 genes, both of which are involved in homologous recombination and DNA repair. To elucidate the physiological role of RAD51 protein, the gene was targeted in embryonic stem (ES) cells. Mice heterozygous for the Rad51 null mutation were intercrossed and their offspring were genotyped. There were no homozygous (Rad51-/-) pups among 148 neonates examined but a few Rad51-/- embryos were identified when examined during the early stages of embryonic development. Doubly knocked-out ES cells were not detected under conditions of selective growth. These results are interpreted to mean that RAD51 protein plays an essential role in the proliferation of cell. The homozygous Rad51 null mutation can be categorized in cell-autonomous defects. Pre-implantational lethal mutations that disrupt basic molecular functions will thus interfere with cell viability.