Genetic loci affecting body weight and fatness in a C57BL/6J x PWK/PhJ mouse intercross

Abstract

To determine the genetic variation that contributes to body composition in the mouse, we interbred a wild-derived strain (PWK/PhJ; PWK) with a common laboratory strain (C57BL/6J; B6). The parental, F(1), and F(2) mice were phenotyped at 18 weeks old for body weight and composition using dual-energy X-ray absorptiometry (DEXA). A total of 479 (244 male and 235 female) F(2) mice were genotyped for 117 polymorphic markers spanning the autosomes. Twenty-eight suggestive or significant linkages for four traits (body weight, adjusted lean and fat weight, and percent fat) were detected. Of these, three QTLs were novel: one on the proximal portion of Chr 5 for body weight (Bwq8; LOD = 4.7), one on Chr 3 for lean weight (Bwtq13; LOD = 3.6), and one on Chr 11 for percent fat (Adip19; LOD = 5.8). The remaining QTLs overlapped previously identified linkages, e.g., Adip5 on Chr 9. One QTL was sex-specific (present in males only) and seven were sex-biased (more prominent in one sex than the other). Most alleles that increased body weight were contributed by the B6 strain, and most alleles that increased percent fat were contributed by the PWK strain. Eight pairs of interacting loci were identified, none of which exactly overlapped the main-effect QTLs. Many of the QTLs found in the B6 x PWK cross map to the location of previously reported linkages, suggesting that some QTLs are common to many strains (consensus QTLs), but three new QTLs appear to be particular to the PWK strain. The location and type of QTLs detected in this new cross will assist in future efforts to identify the genetic variation that determines the ratio of lean to fat weight as well as body size in mice.

Fig. 1

Genome scan results of an F₂ intercross between B6 and PWK inbred mouse strains. The interval maps show body weight, lean weight, fat weight, and percent fat (sex is an additive covariate for these analyses, and body weight was a covariate for lean and fat weight). The three horizontal lines represent LOD thresholds at genome-wide significant level (p < 0.01 and p < 0.05), and suggestive level (p < 0.63), respectively, as determined by 1000 permutation tests

Fig. 2

Effect plot for the interaction of a sex-specific QTL on chromosome 11. Genotypes B/B, B/P, and P/P represent B6 homozygous, B6/PWK heterozygous, and PWK homozygous, respectively

Fig. 3

Plots of pairwise interactions. Chromosome number and peak position in cM are indicated for each QTL. Freestanding text = interaction LOD score and percentage of trait variance accounted for