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 α/β 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.
Copyright © 1997 Cell Press.
, Vol 7, 653-665, November 1997
Article
Growth Retardation and Leaky SCID Phenotype of Ku70-Deficient Mice
1The Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
2Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
3The Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115, USA
4Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
5Howard Hughes Medical Institute, Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA
6Department of Medicine, Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Corresponding author
Frederick W. Alt
617 355 7290 (phone)
617 730 0432 (fax)
alt@rascal.med.harvard.edu
Summary
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