The mutation of the LEW.1AR1-iddm rat maps to the telomeric end of rat chromosome 1.
The mutation of the LEW.1AR1-iddm rat maps to the telomeric end of rat chromosome 1.
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LEW.1AR1-iddm 大鼠的突变定位于大鼠 1 号染色体的端粒末端。
DOI：
10.1007/s00335-008-9102-4
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Wedekind,Dirk
中科院分区：
文献类型：
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作者：
Weiss,Heike;Arndt,Tanja;Jörns,Anne;Lenzen,Sigurd;Cuppen,Edwin;Hedrich,HansJ;Tiedge,Markus;Wedekind,Dirk
LEW.1AR1-iddmrat是一种常染色体隐性遗传的人类1型糖尿病（T1DM）动物模型。在BN回交队列中，T1DM易感位点可定位于主要组织相容性复合体区域（Iddm1）的第20号染色体（RNO）和第1号染色体（Iddm8、Iddm9）。在本研究中，研究了不同易感区对糖尿病抗性PAR菌株回交群体的影响。取130只N2大鼠[（PAR × LEW.1AR1-iddm） × LEW.1AR1-iddm]进行血糖监测，并进行连锁分析。16%的PAR回交动物患上了T1DM。遗传分析显示，RNO20p12的MHC区域与T1DM有显著联系。与BN回交队列的连锁分析相比，在RNO1上只能鉴定出一个T1DM的易感位点。RNO1上的这个易感区与iddm8对应的端粒端相对应。89%的糖尿病PAR回交动物为iddm8纯合子。在PAR回交队列中，iddm9糖尿病易感区与糖尿病无关联。本研究数据证明，LEW.1AR1-iddmrat中导致T1DM的突变位于与iddm8对应的RNO1端粒端。
The LEW.1AR1-iddmrat is an animal model of human type 1 diabetes mellitus (T1DM) with an autosomal recessive mode of inheritance. T1DM susceptibility loci could be localized on chromosome (RNO) 20 in the major histocompatibility complex region (Iddm1) and on RNO1 (Iddm8,Iddm9) in a BN backcross cohort. In this study the impact of the different susceptibility regions on diabetes development was investigated in a backcross population of the diabetes-resistant PAR strain. A cohort of 130 [(PAR × LEW.1AR1-iddm) × LEW.1AR1-iddm] N2 rats was monitored for blood glucose and analyzed by linkage analysis. Sixteen percent of the PAR backcross animals developed T1DM. Genetic analysis revealed significant linkage to T1DM in the MHC region on RNO20p12. In contrast to the linkage analysis of the BN backcross cohort, only one susceptibility locus for T1DM could be identified on RNO1. This susceptibility region on RNO1 mapped to the telomeric end corresponding toIddm8. Eighty-nine percent of diabetic PAR backcross animals were homozygous forIddm8. TheIddm9diabetes susceptibility region showed no linkage to diabetes in the PAR backcross cohort. The data of this study provide evidence that the mutation leading to T1DM in the LEW.1AR1-iddmrat is located at the telomeric end of RNO1 corresponding toIddm8.