title: Xrcc2 is required for genetic stability, embryonic neurogenesis and viability in mice.
abstract: Repair of DNA damage by homologous recombination has only recently been established as an important mechanism in maintaining genetic stability in mammalian cells. The recently cloned Xrcc2 gene is a member of the mammalian Rad51 gene family, thought to be central to homologous recombination repair. To understand its function in mammals, we have disrupted Xrcc2 in mice. No Xrcc2(-/-) animals were found alive, with embryonic lethality occurring from mid-gestation. Xrcc2(-/-) embryos surviving until later stages of embryogenesis commonly showed developmental abnormalities and died at birth. Neonatal lethality, apparently due to respiratory failure, was associated with a high frequency of apoptotic death of post- mitotic neurons in the developing brain, leading to abnormal cortical structure. Embryonic cells showed genetic instability, revealed by a high level of chromosomal aberrations, and were sensitive to gamma-rays. Our findings demonstrate that homologous recombination has an important role in endogenous damage repair in the developing embryo. Xrcc2 disruption identifies a range of defects that arise from malfunction of this repair pathway, and establishes a previously unidentified role for homologous recombination repair in correct neuronal development.
authors: Medical Research Council, Radiation and Genome Stability Unit and Mammalian Genetics Unit, Harwell, Oxfordshire OX11 0RD, UK.
authors: B
authors: B
authors: Deans
authors: C S
authors: CS
authors: Griffin
authors: M
authors: M
authors: Maconochie
authors: J
authors: J
authors: Thacker
mesh_terms: D000818:Animals; D017209:Apoptosis; D001755:Blastocyst / Q000166:cytology* / Q000502:physiology; D002678:Chimera; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005314:Embryonic and Fetal Development / Q000235:genetics*; D005313:Fetal Death; D005838:Genotype; D051379:Mice; D018345:Mice, Knockout; D009420:Nervous System / Q000196:embryology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D016133:Polymerase Chain Reaction; D013234:Stem Cells
chemical_list: D004268:DNA-Binding Proteins; C491866:Xrcc2 protein, mouse