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

来源：

SCIENCE | 1994年 / 266卷 / 5184期

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

页码：450 / 455

页数：6

共 68 条

[1] SUCCESSFUL ENGRAFTMENT OF HUMAN POSTNATAL THYMUS IN SEVERE COMBINED IMMUNE DEFICIENT (SCID) MICE - DIFFERENTIAL ENGRAFTMENT OF THYMIC COMPONENTS WITH IRRADIATION VERSUS ANTI-ASIALO GM-1 IMMUNOSUPPRESSIVE REGIMENS [J].