Genetic Architecture of Body Fat Composition in Mice

Abstract

Body fat composition is a quantitative measure of obesity, a major health concern in humans. Laboratory mice are considered an excellent model for dissecting the genetic basis of obesity due to the genetic variation present in inbred strains for body size and fat composition, as well as their historical use as a model organism for human disease studies. To identify the loci controlling fat pad weights and body weight in mice, we performed a quantitative trait loci (QTL) analysis of 513 (SM/J x NZB/BINJ) F2 individuals fed a high-fat diet for 14 weeks. Our analysis separated fat composition genetic effects from those affecting overall body sizes in mouse. Composite interval mapping (CIM) results showed that body weight was conditioned by three major additive QTLs, explaining 3 to 30% of the phenotypic variation. One significant QTL on chromosome 19 conditioned all fat pads with the exception of the inguinal fat weight, which was controlled by a different QTL also on chromosome 19. Significant QTLs associated with fat compositions were detected on chromosomes 17 and 19 and differed from those of body weight. The fat pad QTLs also showed mainly additive gene effects and they explained 2 to 7% of variation in fat composition. Joint analysis of correlated traits detected five additional large effect QTLs on five different linkage groups. These findings have indicated that fat composition and body weight in mouse are conditioned by one to three major additive genes and can therefore be potentially manipulated in controlling obesity.