Major quantitative trait locus on chromosome 2 for glucose tolerance in diabetic SMXA-5 mouse established from non-diabetic SM/J and A/J strains
Major quantitative trait locus on chromosome 2 for glucose tolerance in diabetic SMXA-5 mouse established from non-diabetic SM/J and A/J strains
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DOI：
10.1007/s00125-005-0121-3
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发表时间：
2006-03-01
期刊：
影响因子：
8.2
通讯作者：
Horio, F
中科院分区：
文献类型：
--
作者：
Kobayashi, M;Io, F;Horio, F
目的/假设：SMXA-5小鼠是由非糖尿病SM/J和A/J品系建立的SMXA重组近交系之一，是以中度糖耐量受损和高胰岛素血症为特征的多基因2型糖尿病模型。喂食高脂肪饮食会使糖尿病患者的这些特征恶化。这项研究的目的是剖析SMXA-5基因组A/J区中影响糖尿病相关性状的糖尿病致病基因。材料和方法：对饲喂高脂饲料的(SM/JxSMXA-5)F-2杂交小鼠进行糖尿病相关性状和肥胖的数量性状基因座(QTL)分析。为了验证本研究中定位的负责基因座的功能，我们构建了一个同源基因株，并对其与糖尿病相关的特征进行了表征。结果：在第2染色体上定位了一个控制糖耐量、空腹血糖浓度和体重指数的主效QTL。该基因座位于D2Mit15附近，在糖耐量试验中，120min血糖浓度的优势数对数最高(12.6)，命名为T2dm2sa。T2dm2sa的糖尿病等位基因起源于A/J株。Sm.A-T2dm2sa是一株将A/J基因组T2dm2sa区域导入Sm/J的同源菌株，表现出明显的糖耐量受损和高胰岛素血症。结论/解释：SM.A-T2dm2sa小鼠糖耐量受损的发展证实了F-2杂交小鼠糖尿病相关性状的QTL分析结果。本研究结果提示，在非糖尿病A/J和SM/J小鼠基因组中存在潜在的致糖尿病基因座，这些基因座的共存导致SMXA-5和SM.A-T2dm2sa小鼠糖耐量受损。
Aims/hypothesis: The SMXA-5 mouse is one of the SMXA recombinant inbred substrains established from the non-diabetic SM/J and A/J strains, and is a model for polygenic type 2 diabetes, characterised by moderately impaired glucose tolerance and hyperinsulinaemia. These diabetic traits are worsened by feeding a high-fat diet. The aim of this study was to dissect the diabetogenic loci in the A/J regions of the SMXA-5 genome that contribute to diabetes-related traits. Materials and methods: We analysed the quantitative trait loci (QTL) for diabetes-related traits and obesity in (SM/JxSMXA-5)F-2 intercross mice fed a high-fat diet. To verify the function of the responsible locus that was mapped in the present study, we constructed a congenic strain and characterised its diabetes-related traits. Results: A major QTL for glucose tolerance, free-fed blood glucose concentration and BMI was mapped on chromosome 2. This locus existed near D2Mit15, with the highest logarithm of the odds score (12.6) for glucose concentration at 120 min in a glucose tolerance test, and was designated T2dm2sa. The diabetogenic allele of T2dm2sa originated in the A/J strain. SM.A-T2dm2sa, a congenic strain that introgressed the T2dm2sa region of A/J genome into SM/J, exhibited overt impaired glucose tolerance and hyperinsulinaemia. Conclusions/interpretation: The development of impaired glucose tolerance in SM.A-T2dm2sa mice confirmed the results of QTL analysis for diabetes-related traits in F-2 intercross mice. The present results suggest that there are latent diabetogenic loci in the genomes of non-diabetic A/J and SM/J mice, and that the coexistence of these loci, including T2dm2sa, causes impaired glucose tolerance in SMXA-5 and SM.A-T2dm2sa mice.