TRANSGENIC MOUSE MODELS FOR STUDYING MUTATIONS IN-VIVO - APPLICATIONSIN AGING RESEARCH

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 recover the plasmids into E. coli h ost cells. A positive selection system, permitting only E. coli cells with a lacZ mutated plasmid to grow, allows for the accurate determina tion of mutation frequencies as the ratio of mutant colonies versus th e total number of transformants, i.e., the total number of plasmid cop ies recovered. Results obtained from a life span study of plasmid mice with vector clusters on chromosome 3 and 4 indicated age-related muta tion accumulation in the liver, but not in the brain. Comparison of th e mutational spectra revealed a significantly larger proportion of lar ge size-change mutations in liver than in brain.