Genetics, Vol 125, 167-174, Copyright © 1990

INVESTIGATIONS

Genetics of Survival in Mice: Subregions of the Major Histocompatibility Complex

R. Gelman, A. Watson, E. Yunis and R. M. Williams
Dana-Farber Cancer Institute, Harvard School of Public Health, Boston, Massachusetts 02115

In this study of murine survival, 422 F(1) hybrids between DBA/2J (D2) female mice and C57BL/10 (B10) background H-2 congenic male mice (11 strains), 88 F(1) hybrids between B10 female mice and B10 background H-2 congenic male mice (3 strains), and 532 control mice from the 11 parental B10 background H-2 congenic mice were bred over a period of 2 yr. Toward the end of the breeding period there was documentation of Sendai infection in the mouse rooms. All analyses were done separately for the two sexes. Although it did not appear that an unusually high number of mice died during the time the colony was infected with Sendai, there was a highly significant tendency for mice who were younger at the time of the Sendai infection to have shorter survival than mice who were older at that time point. The effect of birth date on survival was approximately as significant as the effect of strain on survival. Hence all analyses of genetic effects on survival were either done within subsets of mice born in the same quarter of a particular year or else included date of birth variables in survival models. Of the 18 possible comparisons of pairs of strains which overlapped in birth dates and differed only in the D end of H-2, five were associated with highly significant survival differences. Of the 11 pairs of strains which overlapped in birth date and differed only in the K end of H-2, none was associated with significant survival differences. In models of survival based on birth date and alleles for one of the four subregions (KAE({beta}), E({alpha}), S, DL), KAE({beta}) alleles were seldom (2/8 models) associated with significant survival difference but the other regions usually were associated with significant survival differences (E({alpha}) in 6/8, S in 8/8, DL in 7/8). The most consistent results in comparing alleles in these models of H-2 subregions were: b was associated with longer survival than s or d or k; q was associated with longer survival than d; and k was associated with longer survival than d. We conclude that it is very important for survival studies to be based on animals bred at approximately the same time, since age differences at the time of an environmental stress may result in significant differences in longevity, even among mice who survive the acute health threat. We also conclude that mice differing genetically only at the H-2 (and perhaps closely linked) loci differ significantly in survival. These data also suggest that the D end of H-2 may have more of an effect on survival than the K end; future experiments in these strains, their hybrids, and other congenic strains will be needed to verify this.

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