Genetic contributions to body weight in mice: relationship of exploratory behavior to weight.
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.


METHODS
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.


CONCLUSIONS
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.
Zhang
Shumin
S
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75235-8898, USA.
Gershenfeld
Howard K
HK
D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight / Q000235:genetics*; D002874:Chromosome Mapping; D004041:Dietary Fats / Q000008:administration & dosage; D004734:Energy Metabolism; D005106:Exploratory Behavior; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D010641:Phenotype; D040641:Quantitative Trait Loci; D015430:Weight Gain
D004041:Dietary Fats