Mouse Models Incorporating Alterations In The Major Tumor Suppressor Genes P53 And P16: Their Use In Screening For Potential Carcinogens, Developing Further Relevant Mouse Models, And Screening For Potential Chemopreventive And Chemotherapetutic Agents

Abstract

This review is primarily a follow up to an initial review on this subject that the authors published 4 years ago [Lubet et al., Exp Lung Res. 2000; 581–593]. The present review gives a brief discussion of certain background points and rationale for development of these specific models, which had been presented in greater detail in the earlier article. In that initial article the authors identified the potential use of mutant mice in screening for carcinogens as well as preventive or therapeutic agents, discussed the relevance of the dominant-negative P53 mutation, as contrasted with knockout P53 mice, and briefly discussed the pros and cons of mice with a germline mutation in tumor suppressor genes in developing mouse models. The primary objective of the present review is to describe more recent studies using mice the dominant-negative P53 mutation as well as to introduce studies with mice with a heterozygous knockout of the P16/Ink4A ARF locus.

Key Words:

• P16
• P53
• carcinogens
• lung cancer
• mice