GENETICS OF DIETARY OBESITY IN AKR J X SWR/J MICE - SEGREGATION OF THE TRAIT AND IDENTIFICATION OF A LINKED LOCUS ON CHROMOSOME-4/

We describe a new multiple gene mouse model of differential sensitivit y to dietary obesity that provides a tool for dissecting the genetic b asis for body composition and obesity. AKR/J and SWR/J male mice, as w ell as male progeny of intercrosses between these strains, were fed a high-fat diet for 12 weeks beginning at 5 weeks of age. Body weight an d energy intake were assessed weekly. At the conclusion of the dietary manipulation, an adiposity index was calculated by dividing the weigh t of seven dissected adipose depots by the carcass weight. AKR/J mice had approximately sixfold greater adiposity than SWR/J mice. Examinati on of the segregation of the adiposity trait in the progeny of crosses between these strains indicates that the trait is determined by a min imum of one to four genetic loci and that there is significant dominan ce of the AKR/J genotype. A preliminary analysis with markers linked t o the known mouse obesity genes ob, db, tub, and fat showed no linkage with these loci. However, a quantitative trait locus was found that m aps distal to the db gene on Chromosome (Chr) 4. This locus has been d esignated dietary obese 1 or Do1.