Colle E, Ono S J, Fuks A, Guttmann R D, Seemayer T A
McGill University-Montreal Children's Hospital Research Institute, Royal Victoria Hospital, Quebec, Canada.
Diabetes. 1988 Oct;37(10):1438-43. doi: 10.2337/diab.37.10.1438.
This study was designed to map the diabetes susceptibility gene(s) associated with the rat major histocompatibility complex (MHC) RT1. We have crossed spontaneously diabetic male rats bearing the recombinant RT1r8 haplotype with female rats of the AC1.1r4 congenic strain. Three diabetic rats were determined to be homozygous for the r4 haplotype by serotyping. The absence of recombination within the MHC was confirmed by inspection of restriction-fragment-length patterns of the diabetic animals and the parental strains. In conjunction with previous breeding studies, this study maps the diabetes susceptibility gene to the right of the RT1-A locus and to the left of the RT1-C locus. A low incidence of diabetes in the F2 (4.5%) emphasizes the multifactorial nature of the susceptibility. The presence of depressed responsiveness of peripheral blood lymphocytes to concanavalin A stimulation increases the prevalence of the overt disease. An unusual feature of the diabetic syndrome in this study is the sparse or absent pancreatic lymphocytic inflammatory response, with true insulitis being a rare finding.
本研究旨在绘制与大鼠主要组织相容性复合体（MHC）RT1相关的糖尿病易感基因图谱。我们将携带重组RT1r8单倍型的自发性糖尿病雄性大鼠与AC1.1r4同基因系的雌性大鼠进行杂交。通过血清分型确定三只糖尿病大鼠为r4单倍型纯合子。通过检查糖尿病动物和亲本菌株的限制性片段长度模式，证实了MHC内没有重组。结合先前的育种研究，本研究将糖尿病易感基因定位到RT1-A基因座右侧和RT1-C基因座左侧。F2代中糖尿病的低发病率（4.5%）强调了易感性的多因素性质。外周血淋巴细胞对刀豆球蛋白A刺激的反应性降低增加了显性疾病的患病率。本研究中糖尿病综合征的一个不寻常特征是胰腺淋巴细胞炎症反应稀少或不存在，真正的胰岛炎是罕见的发现。
