Genetic analysis of the diabetes-prone C57BLKS/J mouse strain reveals genetic contribution from multiple strains
Genetic analysis of the diabetes-prone C57BLKS/J mouse strain reveals genetic contribution from multiple strains
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DOI：
10.1016/j.bbadis.2006.01.002
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发表时间：
2006-04-01
影响因子：
6.2
通讯作者：
Péterfy, M
中科院分区：
文献类型：
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作者：
Mao, HZ;Roussos, EI;Péterfy, M
C57 BLKS/J（BKS）近交系小鼠品系是广泛使用的2型糖尿病动物模型。在存在糖尿病（db）突变的情况下，肥胖BKS-db小鼠发展为严重的糖尿病。BKS是耐糖尿病的C57 BL/6 J（136）和敏感的DBA/2 J（DBA）菌株之间的遗传复合物，这一事实促进了该菌株中糖尿病易感性的遗传研究。在此基础上，有人假设BKS的糖尿病易感性是由DBA衍生的等位基因赋予的。然而，最近的研究表明，BKS中存在非B6/非DBA遗传物质。为了确定这一遗传成分的起源，我们使用537个微卫星标记生成了BKS的基因组图谱。我们的研究结果表明，除了B6和DBA，BKS包含至少三个其他菌株，包括129，C57 BL/10和一个未知的小鼠品系的等位基因。我们还分析了两个同源菌株，B6-db和BKS-db，这是广泛用于糖尿病易感基因位点的遗传作图。我们确定了几个供体来源的基因组区域，这些同源菌株的产生过程中引入。总之，我们的研究揭示了BKS和相关菌株遗传精细结构的新方面，并有助于在该小鼠模型中鉴定糖尿病易感基因座。(C)2006 Elsevier B. V.保留所有权利。
The C57BLKS/J (BKS) inbred mouse strain is a widely used animal model of type 2 diabetes. In the presence of the diabetes (db) mutation, obese BKS-db mice develop severe diabetes. Genetic studies of diabetes-susceptibility in this strain are facilitated by the fact that BKS is a genetic composite between the diabetes-resistant C57BL/6J (136) and susceptible DBA/2J (DBA) strains. On this basis, it has been hypothesized that diabetes-susceptibility in BKS is conferred by DBA-derived alleles. However, recent studies revealed non-B6/non-DBA genetic material in BKS. To identify the origin of this genetic component, we generated a genomic map of BKS using 537 microsatellite markers. Our results demonstrate that, in addition to B6 and DBA, BKS contains alleles from at least three other strains, including 129, C57BL/10 and an unidentified mouse strain. We also analyzed two congenic strains, B6-db and BKS-db, which are widely used for the genetic mapping of diabetes-susceptibility loci. We identified several donor-derived genomic regions introduced during the generation of these congenic strains. In summary, our study reveals novel aspects of the genetic fine-structure of BKS and related strains and facilitates the identification of diabetes-susceptibility loci in this mouse model. (C) 2006 Elsevier B.V. All rights reserved.