Zhang Shumin, Gershenfeld Howard K
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75235-8898, USA.
Obes Res. 2003 Jul;11(7):828-38. doi: 10.1038/oby.2003.114.
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.
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.
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.
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.
A/J和C57BL/6J小鼠品系在探索行为和高脂饮食下的体重增加方面存在显著差异。我们研究了探索行为对体重的遗传贡献，并测试了影响能量稳态的共享多效性基因座。
研究了分离的（AxB6）F2杂交（n = 514）和（B6AF1xA/J）N2回交（N = 223）群体，对体重和探索行为进行表型分析。通过相关性分析性状之间的关系。通过全基因组扫描剖析体重性状。
发现探索行为与体重之间存在适度的相关性，解释了2%至14%的方差。绘制了在6%脂肪饮食下8周（wgt8）、10周（wgt10）和2周体重增加（第8周和第10周之间的差异）的体重数量性状基因座（QTL）。染色体1上的两个QTL（峰值位于66 cM和100 cM；Bw8q1）分别影响wgt8（优势比的似然性（Lod），3.0和4.4）和wgt10（Lod，2.2和3.4）。在回交中，染色体4上的一个显著QTL（峰值位于66 cM；Bw8q2）影响wgt 8（Lod，3.3）和wgt10（Lod，3.1）。对于2周体重增加，提示性QTL定位于染色体4和6上。染色体6 QTL区域与人类肥胖的7q基因座重叠。对瘦素和NPY基因的品系间序列多态性的搜索未发现结果。
在小鼠中，影响探索活动的基因座在体重调节中起适度作用。某些形式的肥胖可能源于调节正常体重的基因座。
