Exotic mice as models for aging research: Polemic and prospectus

Most gerontological research using rodent models employs inbred strains, or F1 hybrids derived from them, rather than populations of genetically heterogeneous individuals. This study presents the argument that reliance on genetically homogeneous rodents, though sanctioned by tradition, may not be ideal for many sorts of investigations, and that use of heterogeneous mice and rats would allow researchers to reach robust conclusions that were less likely to reflect strain-specific idiosyncrasies. Segregating stocks, bred by backcross, F2 cross, or four-way cross procedures, would be an improvement over inbred and F1 stocks, providing inexpensive, arbitrarily large, and reproducible populations of genetically diverse test subjects. These stocks would not, however, recapture allelic variations that are likely to have been lost when wild-trapped mice and rats are selected inadvertently over dozens of generations for breeding success in laboratory conditions. Development of species pathogen free stocks from wild-trapped progenitors, particularly from populations selected for relevant evolutionary history and physiological characteristics, may be of great value for analysis of aging and late-life pathophysiology.