TRANSGENIC MOUSE MODELS FOR STUDYING MUTATIONS IN-VIVO - APPLICATIONSIN AGING RESEARCH (VOL 98, PG 189, 1997)

To study mutation accumulation in the DNA of somatic cells and tissues during aging in vivo, a transgenic mouse model has been constructed. The model harbors plasmid vectors, containing the lacZ reporter gene, integrated head to tail at various chromosomal locations, Procedures h ave been worked out to efficiently recovery the plasmids into E., coli host cells. A positive selection system, permitting only E. coli cell s with a lacZ mutated plasmid to grow, allows for the accurate determi nation of mutation frequencies as the ratio of mutant colonies versus the total number of transformants, i.e., the total number of plasmid c opies recovered. Results obtained from a life span study of plasmid mi ce with vector clusters on chromosome 3 and 4 indicated age-related mu tation accumulation in the liver, but not in the brain. Comparison of the mutational spectra revealed a significantly larger proportion of l arge size-change mutations in liver than in brain. (C) 1997 Elsevier S cience Ireland Ltd.