J. Vijg et al., TRANSGENIC MOUSE MODELS FOR STUDYING MUTATIONS IN-VIVO - APPLICATIONSIN AGING RESEARCH (VOL 98, PG 189, 1997), Mechanism of ageing and development, 99(3), 1997, pp. 257-271
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.