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TRAITS THAT INFLUENCE LONGEVITY IN MICE
Edmond J. Yunis 1, Ada L. M. Watson 2, Rebecca S. Gelman 3, Sherrill J. Sylvia 2, Roderick Bronson 4, and Martin E. Dore 5
1 Dana-Farber Cancer Institute, Harvard Medical School Boston,
Massachusetts 02115
2 Dana-Farber Cancer Institute, Boston, Massachusetts 02115
3 Dana-Farber Cancer Institute, Harvard School of Public Health
Boston, Massachusetts 02115
4 Tufts University School of Veterinary Medicine, Boston, Massachusetts
02115
5 Harvard Medical School, Boston, Massachusetts 02115
Analysis of genetic interactions in the segregating backcross [(C57BL/6 x DBA/2)F1 x DBA/2] mice revealed influences of genetic and environmental factors on life span. Using determinants of coat color (brown locus of chromosome 4 and dilute locus of chromosome 9), serologically determined H-2 antigens (chromosome 17 ) and sex as genetic markers, we studied the effects of these genes on longevity. The results suggested that genes in the brown locus (b) segment of chromosome 4, genes in a segment of the sex chromosomes and, to a more limited extent, genes in the segment of chromosome 17 which contains the H-2 haplotype all influenced longevity. The coat color (b locus) segment of chromosome 4 was associated with life span predominantly in females, whereas the chromosome 17 (H-2 haplotype) segment was associated with longer life primarily in males. The dilute locus d segment on chromosome 9 did not affect life span. Longevity appears to be influenced by interactions between genes in the chromosomal segment carrying H-2, those in the b segment, gender and the month of birth. Greater heterozygosity at the loci studied was associated with longer life span. Histopathological findings on mice that died at or after 28 months of age were comparable for all genetic combinations except that there was an increased frequency of lymphoma in females and an increased frequency of amyloidosis in males. Our analysis emphasizes the need for comprehensive studies of aging and longevity that would simultaneously determine the effects of several genetic regions and their interactions with the environment with respect to possible causes of death.
Submitted on April 19, 1984Accepted on August 24, 1984
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