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Science 21 October 1994:
Vol. 266. no. 5184, pp. 450 - 455
DOI: 10.1126/science.7524150
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Articles

Science, Vol 266, Issue 5184, 450-455
Copyright © 1994 by American Association for the Advancement of Science

articles

Rescue of T cell-specific V(D)J recombination in SCID mice by DNA-damaging agents

JS Danska, F Pflumio, CJ Williams, O Huner, JE Dick, and CJ Guidos

Division of Surgical Research, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.

Assembly of antigen receptor V (variable), D (diversity), and J (joining) gene segments requires lymphocyte-specific genes and ubiquitous DNA repair activities. Severe combined immunodeficient (SCID) mice are defective in general double-strand (ds) DNA break repair and V(D)J coding joint formation, resulting in arrested lymphocyte development. A single treatment of newborn SCID mice with DNA-damaging agents restored functional, diverse, T cell receptor beta chain coding joints, as well as development and expansion of thymocytes expressing both CD4 and CD8 coreceptors, but did not promote B cell development. Thymic lymphoma developed in all mice treated with DNA-damaging agents, suggesting an interrelation between V(D)J recombination, dsDNA break repair, and lymphomagenesis.


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