Gene mutations have been implicated in the etiology of cancer, develop
mental anomalies, genetic disease and aging. Many different methods fo
r mutation detection have been developed and applied to obtain a more
fundamental insight in the chain of molecular events that ultimately l
ead to mutations. Most of these methods, however, can only be applied
to cultured cells and therefore do not allow comparative analysis of m
utations 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 study
ing, in different organs and tissues, spontaneous or induced mutations
. Such models allow study of the induction of DNA damage, repair, muta
genesis and carcinogenesis in one animal system. Accordingly, results
obtained may ultimately provide greater insight into the chain of even
ts from in vivo exposure to genotoxic agents to mutations and their ul
timate physiological endpoints. In addition to their use in fundamenta
l research, transgenic animal mutation models find a major application
in the field of genetic toxicology testing, in particular with respec
t to organ specificity.