Targeted Disruption of the Rad51 Gene Leads to Lethality in Embryonic Mice

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 93; no. 13; pp. 6236 - 6240
• Main Authors: Tsuzuki, Teruhisa, Fujii, Yoshimitsu, Sakumi, Kunihiko, Tominaga, Yohei, Nakao, Kazuki, Sekiguchi, Mutsuo, Matsushiro, Aizo, Yoshimura, Yasuhide, Morita, Takashi
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 25.06.1996; National Acad Sciences; National Academy of Sciences
• Subjects: Alleles; Animals; Base Sequence; Cell Line; Cell lines; DNA; DNA probes; DNA-Binding Proteins - genetics; Embryonic Development - genetics; Embryos; Feeder cells; Female; Genes; Genes, Lethal; Genetic mutation; Genetics; Genotypes; Heterozygote; Homozygote; Male; Mice; Mice, Inbred C57BL - embryology; Molecular Sequence Data; Mutation; Pregnancy; Proteins; Rad51 Recombinase; Rodents; Somatic cells
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.93.13.6236

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.