USE OF TRANSGENIC MOUSE MODELS FOR STUDYING SOMATIC MUTATIONS IN AGING

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.