Type 2 diabetes mouse model TallyHo carries an obesity gene on chromosome 6 that exaggerates dietary obesity
Type 2 diabetes mouse model TallyHo carries an obesity gene on chromosome 6 that exaggerates dietary obesity
复制标题
DOI：
10.1152/physiolgenomics.00197.2004
复制
发表时间：
2005-07-14
影响因子：
4.6
通讯作者：
Naggert, JK
中科院分区：
文献类型：
--
作者：
Kim, JH;Stewart, TP;Naggert, JK
Tallyho(Th)小鼠品系是2型糖尿病伴肥胖的多基因模型。对F1代[C57BL/6J(B6)XTH]和TH小鼠回交后代的遗传分析将一个数量性状基因座(QTL)定位到6号染色体上，命名为TH相关体重2(Tabw2)。TH衍生等位基因与体重增加有关。作为鉴定肥胖QTL分子基础的第一步，我们在B6遗传背景上构建了一个小鼠的同源品系，该品系携带来自TH小鼠的包含TABW2的基因组区域。纯合子Tabw2(B6。与对照组(B6)相比，饲喂饲料的TH-TABW2/TABW2表现出轻微但显著的体重、体脂和血浆瘦素水平。TH-+/+)。当动物被维持在高脂肪和高蔗糖(HFS)饮食中时，这种差异加剧。Tabw2同源基因小鼠的饮食诱导肥胖伴随着高瘦素血症、轻度高胰岛素血症、糖耐量受损以及胰岛素注射引起的脂肪组织葡萄糖摄取减少。用B6杂交F2代饲喂HFS日粮。在TH-Tab2/+小鼠中，我们能够将Tabw2肥胖易感基因座的图谱位置细化到从标记D6Mit102远端延伸的15 cM区域(95%可信区间)。综上所述，Tabw2同源基因小鼠是一种新的饮食诱导肥胖的动物模型，对基因-饮食相互作用的研究具有重要价值。
The TallyHo (TH) mouse strain is a polygenic model for Type 2 diabetes with obesity. Genetic analysis in backcross progeny from a cross between F1 [C57BL/6J (B6) X TH] and TH mice mapped a quantitative trait locus (QTL) named TH-associated body weight 2 (tabw2) to chromosome 6. The TH-derived allele is associated with increased body weight. As a first step to identify the molecular basis of this obesity QTL, we constructed a congenic line of mice on the B6 genetic background that carries a genomic region from TH mice containing tabw2. Congenic mice homozygous for tabw2 ( B6. TH-tabw2/tabw2) fed a chow diet exhibited slightly, but significantly, higher body weight and body fat and plasma leptin levels compared with controls ( B6. TH-+/+). This difference was exacerbated when the animals were maintained on a high-fat and high-sucrose (HFS) diet. The diet-induced obesity in tabw2 congenic mice is accompanied by hyperleptinemia, mild hyperinsulinemia, impaired glucose tolerance, and reduced glucose uptake in adipose tissue in response to insulin administration. Using F2 progeny fed a HFS diet from an intercross of B6. TH-tabw2/+ mice, we were able to refine the map position of the tabw2 obesity susceptibility locus to a 15-cM region (95% confidence interval) extending distally from the marker D6Mit102. In summary, tabw2 congenic mice are a new animal model for diet-induced obesity that will be valuable for the study of gene-diet interactions.