Theories on the causes of aging, based on the accumulation of somatic
mutations in tissues of an organism, were formulated decades ago, but
remain insufficiently tested. Transgenic animals, equipped with integr
ated bacterial reporter genes that can be efficiently rescued from tot
al genomic DNA of all tissues and organs, represent ideal tools for in
vestigating the types and frequencies of spontaneous mutants accumulat
ing during aging. The first of such systems, based on the transgenic i
ntegration of bacteriophage lambda shuttle vectors that contain the ba
cterial lacZ gene as mutational target, was constructed in our laborat
ory and is now routinely used. Results obtained with this and the rela
ted LacI system that are relevant for the somatic mutation theory of a
ging will be discussed. One conclusion is that, due to the nature of t
he transgene, lambda-based systems have the disadvantage that deletion
type mutations are underrepresented in comparison to point mutations.
To overcome those limitations, we constructed a new transgenic mouse
model carrying a pUR288 plasmid shuttle vector with the lacZ reporter
gene. Some preliminary data obtained with this model serve to illustra
te its potential use to extensively test the somatic mutation theory o
f aging.