Gonzalez A, Katz J D, Mattei M G, Kikutani H, Benoist C, Mathis D
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique/INSERM, Strasbourg, France.
Immunity. 1997 Dec;7(6):873-83. doi: 10.1016/s1074-7613(00)80405-7.
Autoimmune diabetes in both the human and the nonobese diabetic mouse has elaborate genetics; in the latter case, the disease is influenced by at least 15-20 loci. We anticipated that the genetics would be simpler in the BDC2.5 T cell receptor transgenic mouse model of diabetes, wherein many T cells express a particular diabetogenic specificity. Initiation of insulitis in this model was the same on the two genetic backgrounds analyzed, but the kinetics and penetrance of diabetes were strikingly different, permitting us to focus on genetic influences during a defined window of disease progression. The differences correlated with variations in five genomic intervals, certain ones of which have been previously implicated in susceptibility to autoimmune disease. This reductionist approach indeed simplified the analysis of diabetes susceptibility loci.
人类和非肥胖糖尿病小鼠中的自身免疫性糖尿病都有复杂的遗传学特征；在后一种情况下，该疾病受至少15 - 20个基因座的影响。我们预计，在糖尿病的BDC2.5 T细胞受体转基因小鼠模型中，遗传学特征会更简单，在该模型中许多T细胞表达特定的致糖尿病特异性。在分析的两种遗传背景下，该模型中胰岛炎的起始情况相同，但糖尿病的动力学和发病率却显著不同，这使我们能够关注疾病进展特定阶段的遗传影响。这些差异与五个基因组区间的变异相关，其中某些区间先前已被认为与自身免疫性疾病易感性有关。这种简化方法确实简化了对糖尿病易感基因座的分析。
