J. Vijg et al., TRANSGENIC MOUSE MODELS FOR STUDYING MUTATIONS IN-VIVO - APPLICATIONSIN AGING RESEARCH, Mechanism of ageing and development, 98(3), 1997, pp. 189-202
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.