Pathobiology of aging mice and GEM: background strains and experimental design.
The use of induced and spontaneous mutant mice and genetically engineered mice (and combinations thereof) to study cancers and other aging phenotypes to advance improved functional human life spans will involve studies of aging mice. Genetic background contributes to pathology phenotypes and to causes of death as well as to longevity. Increased recognition of expected phenotypes, experimental variables that influence phenotypes and research outcomes, and experimental design options and rationales can maximize the utility of genetically engineered mice (GEM) models to translational research on aging. This review aims to provide resources to enhance the design and practice of chronic and longevity studies involving GEM. C57BL6, 129, and FVB/N strains are emphasized because of their widespread use in the generation of knockout, transgenic, and conditional mutant GEM. Resources are included also for pathology of other inbred strain families, including A, AKR, BALB/c, C3H, C57L, C58, CBA, DBA, GR, NOD.scid, SAMP, and SJL/J, and non-inbred mice, including 4WC, AB6F1, Ames dwarf, B6, 129, B6C3F1, BALB/c,129, Het3, nude, SENCAR, and several Swiss stocks. Experimental strategies for long-term cross-sectional and longitudinal studies to assess causes of or contributors to death, disease burden, spectrum of pathology phenotypes, longevity, and functional healthy life spans (health spans) are compared and discussed.
Johns Hopkins University, 733 North Broadway, BRB Ste 851, Baltimore, MD 21205, USA. cbrayton@jhmi.edu
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D000375:Aging / Q000473:pathology*; D000818:Animals; D005818:Genetic Engineering; D006801:Humans; D008136:Longevity / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D010641:Phenotype; D012107:Research Design; D016019:Survival Analysis