Fine mapping of a QTL region with large effects on growth and fatness on mouse chromosome 2

We combined the use of a congenic line and recombinant progeny testing (RPT) to characterize and fine map a previously identified region of distal mouse chromosome 2 (MMU2) harboring quantitative trait loci (QTL) with large effects on growth and fatness. The congenic line [M16i.B6-(D2Mit306-D2Mit52); MB2] was created using an inbred line (M16i) derived from a line that had undergone long-term selection for rapid weight gain (M16) as the recipient for an approximately 38-cM region on MMU2 from the inbred line C57BL/6J. A large F2 cohort (1,200 mice) originating from a cross between MB2 and M16i was created, and 40 F2 males with defined recombinations within the QTL region were used to produce 665 segregating progeny. Linkage analysis of the F2 population detected QTL with very large effects on body weight, body fat, lean tissue mass, bone mineral density, and liver weight. Confidence intervals of the QTL were narrowed to regions of 1.5-4.5 cM. Analysis of progeny of the recombinant F2 males confirmed the existence of the QTL and further contributed to localization of their map positions. These efforts confirmed the presence of QTL with major effect on MMU2, narrowed the estimated region harboring the QTL from 38 to 12 cM, and further characterized phenotypic effects of the QTL, effectively culminating in a significantly decreased pool of positional candidate genes potentially representing these genes controlling predisposition to growth and fatness.