The p53-deficient mouse: A model for basic and applied cancer studies

被引:207
作者
Donehower, LA
机构
[1] Division of Molecular Virology, Baylor College of Medicine, Houston, TX 77030, One Baylor Plaza
关键词
gene targeting; knockout; Li-Fraumeni syndrome; mouse; p53; tumor model; tumor suppressor;
D O I
10.1006/scbi.1996.0035
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Inactivation of the p53 gene in the germline of mice by gene targeting has provided researchers with a model similar in many respects to the analogous human inherited cancer predispositian Li-Fraumeni syndrome. The viability of p53 null mice has allowed unexpected opportunities to study the rob of p53 in many different in-vivo and in-vitro contexts. Null (p53-/-) mice have an average time to tumor development of 4.5 months, while half of the heterozygous (p53+/-) mice develop tumors by 18 months. The p53-deficient mice have been particularly valuable in examining the effects of p53 loss on tumor progression. In addition, the mice hold significant promise as tools to assess carcinogens, teratogens, chemopreventative agents, and cancer therapeutic regimens.
引用
收藏
页码:269 / 278
页数:10
相关论文
共 73 条
[1]   P53 CONTROLS BOTH THE G(2)/M AND THE G(1) CELL-CYCLE CHECKPOINTS AND MEDIATES REVERSIBLE GROWTH ARREST IN HUMAN FIBROBLASTS [J].
AGARWAL, ML ;
AGARWAL, A ;
TAYLOR, WR ;
STARK, GR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (18) :8493-8497
[2]   HIGH-FREQUENCY DEVELOPMENTAL ABNORMALITIES IN P53-DEFICIENT MICE [J].
ARMSTRONG, JF ;
KAUFMAN, MH ;
HARRISON, DJ ;
CLARKE, AR .
CURRENT BIOLOGY, 1995, 5 (08) :931-936
[3]  
BLYTH K, 1995, ONCOGENE, V10, P1717
[4]   ALTERING THE GENOME BY HOMOLOGOUS RECOMBINATION [J].
CAPECCHI, MR .
SCIENCE, 1989, 244 (4910) :1288-1292
[5]   GENETIC-ORIGIN OF MUTATIONS PREDISPOSING TO RETINOBLASTOMA [J].
CAVENEE, WK ;
HANSEN, MF ;
NORDENSKJOLD, M ;
KOCK, E ;
MAUMENEE, I ;
SQUIRE, JA ;
PHILLIPS, RA ;
GALLIE, BL .
SCIENCE, 1985, 228 (4698) :501-503
[6]  
CLARKE AR, 1995, ONCOGENE, V11, P1913
[7]   THYMOCYTE APOPTOSIS INDUCED BY P53-DEPENDENT AND INDEPENDENT PATHWAYS [J].
CLARKE, AR ;
PURDIE, CA ;
HARRISON, DJ ;
MORRIS, RG ;
BIRD, CC ;
HOOPER, ML ;
WYLLIE, AH .
NATURE, 1993, 362 (6423) :849-852
[8]   A P53-DEPENDENT MOUSE SPINDLE CHECKPOINT [J].
CROSS, SM ;
SANCHEZ, CA ;
MORGAN, CA ;
SCHIMKE, MK ;
RAMEL, S ;
IDZERDA, RL ;
RASKIND, WH ;
REID, BJ .
SCIENCE, 1995, 267 (5202) :1353-1356
[9]   MICE DEFICIENT FOR P53 ARE DEVELOPMENTALLY NORMAL BUT SUSCEPTIBLE TO SPONTANEOUS TUMORS [J].
DONEHOWER, LA ;
HARVEY, M ;
SLAGLE, BL ;
MCARTHUR, MJ ;
MONTGOMERY, CA ;
BUTEL, JS ;
BRADLEY, A .
NATURE, 1992, 356 (6366) :215-221
[10]   EFFECTS OF GENETIC BACKGROUND ON TUMORIGENESIS IN P53-DEFICIENT MICE [J].
DONEHOWER, LA ;
HARVEY, M ;
VOGEL, H ;
MCARTHUR, MJ ;
MONTGOMERY, CA ;
PARK, SH ;
THOMPSON, T ;
FORD, RJ ;
BRADLEY, A .
MOLECULAR CARCINOGENESIS, 1995, 14 (01) :16-22