TARGETED DISRUPTION OF THE RAD51 GENE LEADS TO LETHALITY IN EMBRYONICMICE

The mouse Rad51 gene is a mammalian homologue of the Escherichia coli recA and yeast RAD51 genes, both of which are involved in homologous r ecombination and DNA repair, To elucidate the physiological role of RA D51 protein, the gene was targeted in embryonic stem (ES) cells, Mice heterozygous for the Rad51 null mutation were inter-crossed and their offspring were genotyped. There were no homozygous (Rad51(-1-)) pups a mong 148 neonates examined but a few Rad51(-1-) embryos were identifie d when examined during the early stages of embryonic development. Doub ly knocked-out ES cells were not detected under conditions of selectiv e growth. These results are interpreted to mean that RAD51 protein pla ys an essential role in the proliferation of cell, The homozygous Rad5 1 null mutation can be categorized in cell-autonomous defects. Pre-imp lantational lethal mutations that disrupt basic molecular functions wi ll thus interfere with cell viability.