LACZ TRANSGENIC MOUSE MODELS - THEIR APPLICATION IN GENETIC TOXICOLOGY

Gene mutations have been implicated in the etiology of cancer, developmental anomalies, genetic disease and aging. Many different methods for mutation detection have been developed and applied to obtain a more fundamental insight in the chain of molecular events that ultimately lead to mutations. Most of these methods, however, can only be applied to cultured cells and therefore do not allow comparative analysis of mutations in various organs and tissues in an intact organism. The main difficulty in studying mutagenesis in chromosomal DNA is to identify and isolate mutated genes with a high efficiency. Here we describe the development and application of LacZ transgenic mouse models for studying, in different organs and tissues, spontaneous or induced mutations. Such models allow study of the induction of DNA damage, repair, mutagenesis and carcinogenesis in one animal system. Accordingly, results obtained may ultimately provide greater insight into the chain of events from in vivo exposure to genotoxic agents to mutations and their ultimate physiological endpoints. In addition to their use in fundamental research, transgenic animal mutation models find a major application in the field of genetic toxicology testing, in particular with respect to organ specificity.