GENES CAUSING SPONTANEOUS OBESITY

本研究的长期目标是探讨心力衰竭的机制。 小鼠的自发性肥胖。之前的工作已经确定了4条染色体 区域(鼠标频率6、7、12和15)或基因座(QTL) 自发性肥胖的BSB小鼠的肥胖。BSB小鼠是由一种 (小鼠×C57BL/6J)F1×B6回交。初步数据显示， 现有的同源小鼠品系证实了CHR上的基因座。7. 会影响肥胖。这项提案目的是确定 这些肥胖基因背后的基因。同基因小鼠品系 在B6上携带Spretus染色体区域作为供体DNA 将创建背景。作为肥胖、血浆的共同QTL 胆固醇和肝脂酶(HL)活性对小鼠肝脏的影响。共发现7株， 已经构建的B6 HL基因敲除将用于检验假设 HL活性的改变决定了这些胆固醇和/或肥胖 精神错乱。BSB与HL KO B6小鼠回交将产生两种动物 HL基因敲除的纯合子和杂合子。染色体上的QTL 7.对两组进行比较和对比。老鼠咯咯叫着。 6、7和1个基因座包括在其90%的可信区间内， 分别是肥胖、肥胖和解偶联蛋白2基因。 对这些候选基因的分子和生化研究将是 执行以测试差异是否可能解释观察到的 对性状的影响。如果在编码部分存在差异 Spretus和B6瘦素，然后是 差异将被测试。6号染色体的基因座仅与 在BSB小鼠身上测量的四个脂肪垫之一。瘦素基因表达水平的研究 四个肥胖垫将被确定为检查它们与 血浆瘦素和脂肪垫大小。他们已经找到了斯普雷特斯 与B6UCP2的2个氨基酸不同，因此UCP2的解偶联活性 将对这些菌株进行检测。

The long-term goal of this research is to investigate the mechanisms of spontaneous obesity in mice. Previous work has identified 4 chromosomal regions (mouse chr. 6,7,12,and 15) or loci (QTLs) that contribute to obesity in spontaneously obese BSB mice. BSB mice were produced by a backcross of (Mus spretus x C57BL/6J) F1 x B6. Preliminary data on an available congenic mouse strains confirm that the locus on chr. 7 affects adiposity. The objective of this present proposal is to identify the genes underlying these obesity loci. Congenic mouse strains carrying the spretus chromosomal regions as donor DNA on the B6 background will be created. As co-incident QTLs for obesity, plasma cholesterol and hepatic lipase (HL) activity on mouse chr. 7 were found, the already constructed B6 HL knockout will used to test the hypothesis that alterations of HL activity determine these cholesterol and/obesity loci. BSB backcrosses with the HL KO B6 mouse will yield animals both homozygous and heterozygous for the HL knock-out. QTLs at chromosome 7; will be compared and contrasted in these two groups. The mouse chr. 6,7, and 1 loci include within their 90 percent confidence intervals, respectively, the obese, tubby, and uncoupling protein 2-genes. Molecular and biochemical studies of these candidate genes will be performed to test whether differences are likely to explain the observed effect on the trait. If there are differences in the coding portion of the spretus and B6 leptin, then the biological consequence of the differences will be tested. The chromosome 6 locus was linked to just one of the four fat pads measured in BSB mice. Leptin mRNA levels in the four fat pads will be determined to examine their correlations with plasma leptin and fat pad sizes. They have already found that spretus and B6 UCP2 differ for 2 amino acids, so uncoupling activity of UCP2 from these strains will be examined.