RESCUE OF T-CELL-SPECIFIC V(D)J RECOMBINATION IN SCID MICE BY DNA-DAMAGING AGENTS

被引:113
作者
DANSKA, JS
PFLUMIO, F
WILLIAMS, CJ
HUNER, O
DICK, JE
GUIDOS, CJ
机构
[1] HOSP SICK CHILDREN, RES INST, DIV IMMUNOL & CANC, TORONTO M5G 1X8, ON, CANADA
[2] UNIV TORONTO, DEPT IMMUNOL, TORONTO, ON, CANADA
[3] HOSP SICK CHILDREN, RES INST, DEPT GENET, TORONTO M5G 1X8, ON, CANADA
[4] UNIV TORONTO, DEPT MOLEC & MED GENET, TORONTO, ON, CANADA
[5] UNIV TORONTO, DEPT IMMUNOL, TORONTO, ON, CANADA
关键词
D O I
10.1126/science.7524150
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 oi 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.
引用
收藏
页码:450 / 455
页数:6
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