LIFE-SPAN AND LESIONS IN GENETICALLY HETEROGENEOUS (4-WAY CROSS) MICE- A NEW MODEL FOR AGING RESEARCH

Genetically heterogeneous animal models provide many advantages for re search on aging but have been used infrequently. We present here lifes pan and lesion data from a study of mice bred as a cross between (AKR/ J x DBA/2J)F-1 females and (C57BL/6J x SJL/J)F-1 males. In such a four -way cross population, each mouse is genetically unique, but replicate populations of essentially similar genetic structure can be generated quickly, at low cost, and of arbitrary size from commercially availab le, genetically stable hybrid parents. We employed a protocol in which mice judged to be severely ill were euthanatized to obtain tissue in optimal condition for necropsy, and we were able to infer a likely cau se of illness in 42 of 44 animals. Malignant lymphoma, including at le ast four histopathologically distinct subtypes, was the most common ca use and was also a frequent incidental finding in mice dying of other causes. Neoplastic disease, benign or malignant, was the sole or a con tributing cause of illness in 90% of the mice for which a cause could plausibly be assigned. A wide range of lethal and nonlethal degenerati ve lesions was also noted. The coefficient of variation for lifespan i n these genetically heterogeneous mice was 26%, similar to that seen i n analyses of recombinant inbred mouse lines. Baseline lifespan and pa thology data on four-way cross mice is a useful prelude to the exploit ation of this rodent model in tests of genetic and mechanistic hypothe ses about aging.