Experiment
C57BL/6J mice were crossed with a new wild-derived strain, POHN. Two new life span QTL
were identified as well as new QTL for metabolic heat production and new body weight QTL. The POHN mouse was captured on the island of Pohnpei in the Federated States of Micronesia and was in 10-14 generations of inbreeding at the time of this study (5%-15% of the original heterozygosity was still present); it is now fully inbred. F1 hybrids were produced by crossing female POHN mice with male C57BL/6J mice; a backcross population (N2) was produced by mating female F1 mice with male POHN mice. Thus, all N2 mice had POHN mitochondrial DNA.
A total of 342 (176 female and 166 male) N2 mice from a backcross of (POHN X C57BL/6) F1 x POHN mice were used in the life-span analysis.
A suggestive QTL, Ls1 (life span 1) was identified at 171.9 Mb on Chr 1, LOD=2.3, p<0.1. A marginal QTL, Ls2 (life span 2) was identified at 63.8 Mb on Chr 4, LOD=1.5, p<0.63. (Fig 5A, Table 1).
However 41 mice died before 400 days (400 days considered short lived). The deaths may not have been related to aging, but to specific early pathologies. These short-lived mice were excluded and QTL analysis was reconducted.
Ls1 became more significant, LOD=3.7, p<.01 and its 95% confidence interval was reduced from 49.5 to 38.5 Mb (147.0-185.5 Mb). There was no such benefit for Ls2. Alleles at Ls1 explained about 3.5% of the varaition in life span for the population that excluded short-lived mice. Alleles at Ls2 explained about 1.6% of the variation. At both loci mice carrying the B6 allele lived longer than those carrying the homozygous (P/P) genotype. Mice with the P/B geneotype at both Ls1 and Ls2 had the longest life span.
Two significant QTL for body weight were identified:
Bwq19, body weight QTL 19, peaked at 69.3 Mb on Chr 2 with a confidence interval between 63.2-113.7 Mb, LOD=5.9, p<0.01 and accounted for 6% of the varaition in body weight among the N2 mice.
Bwq20, body weight QTL 20, peaked at 56.3 Mb on Chr 11 with a confidence interval spanning 42.4-103.3 Mb, LOD=3.1, p<0.05 and accounted for 3.1% of trait variation. Mice homozygous for the POHN allele, both male and female, were significantly lighter weight than heterozygotes. Compared with mice that carry only P alleles at both loci, females with B6 alleles at both loci were 27% heavier; males 24% heavier.
QTL analysis of data from 190 randomly selected N2 mice (103 female and 87 male) between 9 and 12 months of age identified a mariginal QTL for metabolic heat production:
Mhp1, metabolic heat production 1, peaked at 166.1 Mb on Chr 2, LOD=2.2, p<0.63.
Also a suggestive QTL was identified, Mph2 peaking at 98.8 Mb on Chr 4, LOD=3.3, p<0.1.
There was an interaction with sex at each locus. P/B females at Mph1 had significantly lower metabolic heat production than P/P females where the opposite was true at Mph2.
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