Identification of a major locus for islet inflammation and fibrosis in the spontaneously diabetic Torii rat
Identification of a major locus for islet inflammation and fibrosis in the spontaneously diabetic Torii rat
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DOI：
10.1152/physiolgenomics.90214.2008
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发表时间：
2008-09-01
影响因子：
4.6
通讯作者：
Seino, Susumu
中科院分区：
文献类型：
--
作者：
Fuse, Masanori;Yokoi, Norihide;Seino, Susumu
Fuse M，Yokoi N，Shinohara M，Masuyama T，Kitazawa R，Kitazawa S，Seino S.自发性糖尿病大鼠胰岛炎症和纤维化的主要基因定位。PhysIOL基因组学35：96-105,2008。2008年7月8日首次出版；DOI：10.1152/Physiolgenomics.90214.2008。-糖尿病患者胰岛炎症和纤维化的发病机制很大程度上是未知的。自发性糖尿病Torii(SDT)大鼠在疾病发展过程中表现出胰岛及其周围的炎症和纤维化。我们研究了SDT大鼠糖尿病、胰岛炎症和纤维化的遗传因素。我们通过SDT和F344大鼠的杂交产生了F1和F2大鼠，检测了糖尿病的发病情况、糖耐量和胰腺组织学，并对这些性状进行了遗传分析。然后，我们在F344遗传背景上最强的糖尿病基因座上建立了一株携带SDT等位基因的同源菌株，并对胰腺的葡萄糖耐量和组织学进行了表征。F1大鼠表现为糖耐量异常和炎症改变，主要分布在胰岛。对糖尿病的遗传分析确定了3号染色体上的一个主要基因座，命名为Dmsdt1，在该基因座上涉及一个起主导作用的SDT等位基因。糖耐量的QTL分析表明，除了Dmsdt1[D3Mit12附近的对数优势(LOD)5.3]外，还有另外三个座位，分别命名为Dmsdt2(D8Rat46的LOD 4.2)，Dmsdt3(D13Arb5附近的LOD 3.8)和D14Arb18的Dmsdt4(LOD 5.8)。对Dmsdt1的同源菌株的分析表明，主要作用的SDT等位基因会导致胰岛炎症和纤维化。因此，我们在3号染色体上发现了SDT大鼠胰岛炎症和纤维化的主要基因座。对相关基因的识别将有助于深入了解糖尿病的发病机制。
Fuse M, Yokoi N, Shinohara M, Masuyama T, Kitazawa R, Kitazawa S, Seino S. Identification of a major locus for islet inflammation and fibrosis in the spontaneously diabetic Torii rat. Physiol Genomics 35: 96-105, 2008. First published July 8, 2008; doi: 10.1152/physiolgenomics.90214.2008.-The pathogenesis of inflammation and fibrosis in the pancreatic islets in diabetes is largely unknown. Spontaneously diabetic Torii (SDT) rats exhibit inflammation and fibrosis in and around the islets during the development of the disease. We investigated genetic factors for diabetes, islet inflammation, and fibrosis in the SDT rat. We produced F1 and F2 rats by intercross between SDT and F344 rats, examined the onset of diabetes, glucose tolerance, and histology of the pancreas, and performed genetic analysis of these traits. We then established a congenic strain carrying the SDT allele at the strongest diabetogenic locus on the F344 genetic background and characterized glucose tolerance and histology of the pancreas. F1 rats showed glucose intolerance and inflammatory changes mainly in the islets. Genetic analysis of diabetes identified a major locus on chromosome 3, designated Dmsdt1, at which a dominantly acting SDT allele was involved. Quantitative trait locus (QTL) analysis of glucose tolerance revealed, in addition to Dmsdt1 [logarithm of odds (LOD) 5.3 near D3Mit12], three other loci, designated Dmsdt2 (LOD 4.2 at D8Rat46), Dmsdt3 (LOD 3.8 near D13Arb5), and Dmsdt4 (LOD 5.8 at D14Arb18). Analysis of a congenic strain for Dmsdt1 indicates that the dominantly acting SDT allele induces islet inflammation and fibrosis. Thus we have found a major locus on chromosome 3 for islet inflammation and fibrosis in the SDT rat. Identification of the genes responsible should provide insight into the pathogenesis of diabetes.