Targeted disruption of NBS1 reveals its roles in mouse development and DNA repair.
Ataxia-Telangiectasia, Cell-Cycle-Proteins, Cell-Division, Cells-Cultured, DNA, DNA-Repair, Female, G2-Phase, Gamma-Rays, Gene-Targeting, Growth, Immunologic-Deficiency-Syndromes, Lymphoid-Tissue, Lymphoma, Male, Mice, Mice-Knockout, Oocytes, Oogenesis, Protein-Serine-Threonine-Kinases, Radiation-Tolerance, Spermatogenesis, Spermatozoa, SUPPORT-U-S-GOVT-P-H-S, Thymus-Neoplasms
EMBO J 2002 Mar; 21(6):1447-55.
Nijmegen breakage syndrome (NBS) is an autosomal recessive hereditary disease that shares some common defects with ataxia-telangiectasia. The gene product mutated in NBS, named NBS1, is a component of the Mre11 complex that is involved in DNA strand-break repair. To elucidate the physiological roles of NBS1, we disrupted the N-terminal exons of the NBS1 gene in mice. NBS1(m/m) mice are viable, growth retarded and hypersensitive to ionizing radiation (IR). NBS1(m/m) mice exhibit multiple lymphoid developmental defects, and rapidly develop thymic lymphoma. In addition, female NBS1(m/m) mice are sterile due to oogenesis failure. NBS1(m/m) cells are impaired in cellular responses to IR and defective in cellular proliferation. Most systematic and cellular defects identified in NBS1(m/m) mice recapitulate those in NBS patients, and are essentially identical to those observed in Atm(-/-) mice. In contrast to Atm(-/-) mice, spermatogenesis is normal in NBS1(m/m) mice, indicating that distinct roles of ATM have differential requirement for NBS1 activity. Thus, NBS1 and ATM have overlapping and distinct functions in animal development and DNA repair.
Kang, J; Bronson, R T.; and Xu, Y, " Targeted disruption of NBS1 reveals its roles in mouse development and DNA repair." (2002). Faculty Research 2000 - 2009. 368.