Growth Retardation and Leaky SCID Phenotype of Ku70-Deficient Mice

作者：Yansong Gu, Katherine J. Seidl, Gary A. Rathbun, Chengming Zhu, John P. Manis, Nienke van der Stoep, Laurie A. Davidson, Hwei-Ling Cheng, JoAnn Sekiguchi, Karen M. Frank, Patricia Stanhope-Baker, Mark S. Schlissel, David B. Roth, Frederick W. Alt · 发表于：Immunity · 年份：1997 · DOI：10.1016/s1074-7613(00)80386-6 · 被引用次数：463 · 研究领域：DNA Repair Mechanisms、PARP inhibition in cancer therapy、CRISPR and Genetic Engineering

Ku70, Ku80, and DNA-PKcs are subunits of the DNA-dependent protein kinase (DNA-PK), an enzyme implicated in DNA double-stranded break repair and V(D)J recombination. Our Ku70-deficient mice were about 50% the size of control littermates, and their fibroblasts were ionizing radiation sensitive and displayed premature senescence associated with the accumulation of nondividing cells. Ku70-deficient mice lacked mature B cells or serum immunoglobulin but, unexpectedly, reproducibly developed small populations of thymic and peripheral alpha/beta T lineage cells and had a significant incidence of thymic lymphomas. In association with B and T cell developmental defects, Ku70-deficient cells were severely impaired for joining of V(D)J coding and recombination signal sequences. These unanticipated features of the Ku70-deficient phenotype with respect to lymphocyte development and V(D)J recombination may reflect differential functions of the three DNA-PK components.