SPONTANEOUS POLYENDOCRINE AUTOIMMUNE DISEASE

I型(胰岛素依赖型)糖尿病通常与 自身免疫性疾病，如格雷夫斯病，桥本氏甲状腺炎， 爱迪生病和无临床症状的单纯自身抗体 显化。NOD小鼠发生自身免疫性I型糖尿病继发 通过渗入免疫细胞来破坏胰岛β细胞(胰岛炎症)。 在我们的乔斯林，糖尿病的发病率是90%的女性和50%的男性 殖民地。NOD雌性和雄性NOD小鼠的胰岛素炎发生率均为100%。 10周大。胰岛素炎的严重程度是不同的 雌性和雄性NOD小鼠之间。除了I型糖尿病，诺德 小鼠发生自身免疫性甲状腺炎的发病率为18%，肾上腺炎症的发病率为 在我们的殖民地有7%的发病率。与岛炎病变不同的是， 浸润性免疫细胞对组织的损伤较弱(1级)。 NOD小鼠的甲状腺和肾上腺。在我们的结节繁育研究中 对于斯普雷特斯家鼠，我们发现了两种不同的类型 糖尿病、I型前期和II型(非胰岛素依赖型)糖尿病，以及 甲状腺炎发病率较高(bc1女性为47%，bc1女性为33% 男性)和肾上腺炎(Bc1女性83%，Bc1男性54%) 通过渗透免疫细胞造成严重损害。这种动物模型 Bc1[(NODxMus Spretus)F1xNOD]是研究 自身免疫性糖尿病、甲状腺炎和肾上腺炎之间的相互依存关系。 我们的初步研究表明，甲状腺炎可能与 5号染色体D5位点59位点，D7位点位40位点为肾上腺炎 7号染色体，D1Mit 17和D1Mit16上的II型糖尿病 1和15号染色体上的D15Mit 6。 我们建议的研究旨在描述I型和II型糖尿病的特征， 回交动物甲状腺、肾上腺炎症及其遗传学研究 对自身免疫性内分泌疾病的易感性有以下几种方式： A)建立100多只糖尿病bc1[(NODxMus Spretus)F1xNOD] 动物。 B)胰腺、甲状腺和肾上腺的组织学检查 糖尿病和非糖尿病Bc1[(NODxMus Spretus)F1xNOD]动物。 C)SSR(简单序列重复)标记与 胰腺炎、甲状腺炎、肾上腺炎、胰岛素抵抗和II型 Bc1[(NODxMus Spretus)F1xNOD]、BC2(BC1xNOD)和BC3(BC2xNOD)中的糖尿病。

Type I (insulin-dependent) diabetes mellitus is often associated with autoimmune diseases like Graves' disease, Hashimoto's thyroiditis, Addison's disease and simply autoantibodies without clinical manifestation. The NOD mouse develops autoimmune type I diabetes secondary to islet beta cell destruction by infiltrating immune cells (insulitis). The incidence of diabetes is 90% in females and 50% in males in our Joslin colony. The incidence of insulitis is 100% in female and male NOD mice at 10 weeks of age. There is a difference in the severity of insulitis between female and male NOD mice. In addition to type I diabetes, the NOD mouse develops autoimmune thyroiditis at 18% incidence and adrenalitis at 7% incidence in our colony. In contrast to the insulitis lesion, the tissue damage by the infiltrating immune cells was weak (grade 1) in the thyroid and adrenal glands from NOD mice. In our breeding studies of NOD with Mus spretus, a wild mouse strain, we have found two different types of diabetes, pretype I and type II (non-insulin-dependent) diabetes, and a higher incidence of thyroiditis (47% in BC1 females and 33% in BC1 males) and adrenalitis (83% in BC1 females and 54% in BC1 males) with more severe damages by infiltrating immune cells. This animal model of BC1[(NODxMus spretus)F1xNOD] represent a unique opportunity to study the interdependency between autoimmune diabetes, thyroiditis and adrenalitis. Our preliminary studies indicate that thyroiditis is possibly linked to D5Mit 59 locus on chromosome 5, adrenalitis to D7Mit 40 locus on chromosome 7, and type II diabetes to D1Mit 17 and D1Mit16 on chromosome 1 and D15Mit 6 on chromosome 15. Our proposed studies aim to characterize type I and type II diabetes, thyroiditis and adrenalitis in the backcross animals and study the genetic susceptibility to the autoimmune endocrine diseases in the following ways: a) Establishment of 100 more diabetic BC1[(NODxMus spretus)F1xNOD] animals. b) Histological examination of the pancreas, thyroid and adrenal glands of the diabetic and nondiabetic BC1[(NODxMus spretus)F1xNOD] animals. c) Linkage analysis of SSR (simple sequence repeat) markers with insulitis, thyroiditis, adrenalitis, insulin-resistance and type II diabetes in BC1[(NODxMus spretus)F1xNOD], Bc2(BC1xNOD) and BC3(BC2xNOD).