Genetic Contributions to Body Weight in Mice: Relationship of Exploratory Behavior to Weight

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OBJECTIVE: The A/J and C57BL/6J mouse strains differ markedly in their exploratory behavior and their weight gain on a high-fat diet. We examined the genetic contributions of exploratory behavior to body weight and tested for shared, pleiotropic loci influencing energy homeostasis. RESEARCH METHODS AND PROCEDURES: Segregating (AxB6)F2 intercross (n = 514) and (B6AF1xA/J)N2 backcross (N = 223) populations were studied, phenotyping for weight and exploratory behaviors. Relationships among traits were analyzed by correlations. Weight traits were dissected with a genome-wide scan. RESULTS: Modest correlations were found between exploratory behaviors and weight, explaining 2% to 14% of the variance. Quantitative trait loci (QTL) for body weight at 8 weeks (wgt8), 10 weeks (wgt10), and 2-week weight gain (difference between weeks 8 and 10) on a 6% fat diet were mapped. Two QTL on chromosome 1 (peaks at 66 cM and 100 cM; Bw8q1) affected wgt8 [likelihood of the odds ratio (Lod), 3.0 and 4.4] and wgt10 (Lod, 2.2 and 3.4), respectively. In the backcross, a significant QTL on chromosome 4 (peak at 66 cM; Bw8q2) affected wgt 8 (Lod, 3.3) and wgt10 (Lod, 3.1). For 2-week weight gain, suggestive QTL were mapped on chromosomes 4 and 6. The chromosome 6 QTL region overlaps a human 7q locus for obesity. A search for between-strain sequence polymorphisms in the leptin and NPY genes was unrevealing. DISCUSSION: In mice, loci influencing exploratory activity play a modest role in body-weight regulation. Some forms of obesity may emerge from loci regulating normal body weight.