Quantitative Trait Loci that Control Body Weight and Obesity in an F2 Intercross between C57BL/6J and DDD.Cg-Ay Mice

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I have developed a congenic mouse strain for the Ay allele at the agouti locus in an inbred DDD/Sgn strain, DDD.Cg-Ay. DDD.Cg-Ay females are extremely obese and significantly heavier than B6.Cg-Ay females. The objectives of this study were to determine the genetic basis of obesity in DDD.Cg-Ay mice, and to determine whether or not their high body weight was due to the presence of DDD background-specific modifiers. I performed quantitative trait locus (QTL) analyses for body weight and body mass index in two types of F2 mice [F2 Ay (F2 mice carrying the Ay allele) and F2 non-Ay (F2 mice without the Ay allele)] produced by crossing C57BL/6J females and DDD.Cg-Ay males. The results of the QTL analysis of F2 Ay mice were very similar to those obtained for F2 non-Ay mice. It was unlikely that the high body weight of DDD.Cg-Ay mice was due to the presence of specific modifiers. When both F2 datasets were merged and analyzed, four significant body weight QTLs were identified on chromosomes 6, 9, and 17 (two loci) and four significant obesity QTLs were identified on chromosomes 1, 6, 9, and 17. Although the presence of DDD background-specific modifiers was not confirmed, a multifactorial basis of obesity in DDD.Cg-Ay females was thus revealed.