Quantitative trait loci for impaired glucose tolerance in nondiabetic SM/J and A/J mice.
Quantitative trait loci for impaired glucose tolerance in nondiabetic SM/J and A/J mice.
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DOI：
10.1152/physiolgenomics.00027.2008
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发表时间：
2008-09
影响因子：
4.6
通讯作者：
Natsuko Hada;Misato Kobayashi;M. Fujiyoshi;A. Ishikawa;Masako Kuga;M. Nishimura;S. Ebihara;T. Ohno;F. Horio
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文献类型：
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作者：
Natsuko Hada;Misato Kobayashi;M. Fujiyoshi;A. Ishikawa;Masako Kuga;M. Nishimura;S. Ebihara;T. Ohno;F. Horio
从非糖尿病亲本SM/J和A/J小鼠建立的SMXA-5重组近交系发展出糖尿病表型，如葡萄糖耐量受损。SM/J和A/J基因组中致糖尿病基因的组合损害SMXA-5小鼠的葡萄糖耐量。使用（SM/J x SMXA-5）F2小鼠喂养高脂饮食，我们以前检测到的糖尿病基因座，T2 dm 2sa，染色体（Chr）2。该位点的A/J等位基因是糖尿病基因。将A/J的Chr 2区（包括T2 dm 2sa）基因渗入SM/J的SM. A-T2 dm 2sa同源小鼠，表现出明显的糖耐量异常。这些结果表明，SM. A-T2 dm 2sa小鼠由于具有A/J等位基因的T2 dm 2sa和具有SM/J等位基因的未知糖尿病基因座而发展出糖尿病致突变性状。本研究的目的是解剖这些未知的位点，利用数量性状基因座（QTL）分析在（A/J × SM. A-T2 dm 2sa）F2交饲高脂饲料。结果表明，一个高度显着的QTL，T2 dm 4sa，对葡萄糖耐量的Chr 6和一个显着的QTL，T2 dm 5sa，对葡萄糖耐量的Chr 11。这些位点与SM/J等位基因是糖尿病。T2 dm 4sa或T2 dm 5sa的致糖尿效应通过在A/J-6（SM）或A/J-11（SM）同源株中的葡萄糖耐量受损来验证，其中SM/J的Chr 6或Chr 11分别渗入A/J。这些结果表明，糖尿病基因座存在于非糖尿病A/J和SM/J小鼠的基因组中，并表明具有A/J等位基因的T2 dm 2sa和具有SM/J等位基因的T2 dm 4sa和/或T2 dm 5sa在SM. A-T2 dm 2sa小鼠中引起糖耐量受损。
The SMXA-5 recombinant inbred strain, which was established from nondiabetic parental SM/J and A/J mice, develops diabetic phenotypes such as impaired glucose tolerance. The combination of diabetogenic genes in the SM/J and A/J genomes impairs glucose tolerance in SMXA-5 mice. Using (SM/J x SMXA-5)F2 mice fed a high-fat diet, we previously detected a diabetogenic locus, T2dm2sa, on chromosome (Chr) 2. The A/J allele at this locus is diabetogenic. The SM.A-T2dm2sa congenic mouse, in which the Chr 2 region of A/J including T2dm2sa was introgressed into SM/J, showed obviously impaired glucose tolerance. These results indicate that SM.A-T2dm2sa mice develop diabetogenic traits due to T2dm2sa with the A/J allele and unknown diabetogenic loci with the SM/J allele. The aim of this study was to dissect these unknown loci, using quantitative trait locus (QTL) analysis in the (A/J x SM.A-T2dm2sa) F2 intercross fed a high-fat diet. The results revealed a highly significant QTL, T2dm4sa, for glucose tolerance on Chr 6 and a significant QTL, T2dm5sa, for glucose tolerance on Chr 11. These loci with the SM/J allele were diabetogenic. The diabetogenic effect of T2dm4sa or T2dm5sa was verified by the impairment of glucose tolerance in the A/J-6(SM) or A/J-11(SM) consomic strain, in which Chr 6 or Chr 11 of SM/J is introgressed into A/J, respectively. These results demonstrate that diabetogenic loci exist in the genomes of nondiabetic A/J and SM/J mice and suggest that T2dm2sa with the A/J allele and T2dm4sa and/or T2dm5sa with the SM/J allele elicit impaired glucose tolerance in SM.A-T2dm2sa mice.