NOD-H2H4 MICE AS A SENTINEL MODEL FOR AUTOIMMUNE THYROID

描述(摘自调查人员摘要) 自身免疫性甲状腺炎是一种多因素疾病，其中 易感性与环境因素相结合，可诱发疾病。在……里面 人类的甲状腺可能会受到饮食、药物和其他合成物质的影响 化学制品。过量的碘可能是增加的部分原因。 自身免疫性甲状腺炎的患病率。其他环境化学品也可能 有牵连，但几乎没有书面证据表明哪些化学物质 可能牵涉其中。候选污染物包括多环芳烃、 多溴联苯和多氯联苯。传染病病原体 也会引发自身免疫力。在这项提案中，调查人员 将1)开发标准的可重复条件以获得50%的发病率 对NOD.H2h4小鼠的碘加重的自身免疫性甲状腺炎的治疗作用和2)使用 小鼠模型来研究食物中环境化学物质的影响， 工业产品，或感染对自身免疫性甲状腺炎的发展。 甲基胆蒽(MCA)将被用作聚芳烃的一个例子 碳氢化合物，KBrR将用作多溴联苯的例子，以及 茶碱将被用作一种可以提高碘含量的药物的例子 领悟。在目标3中，内毒素(LPS)将被用作 确定感染性病原体在自身免疫中的作用 甲状腺炎。NOD.H2h4小鼠对自身免疫的遗传易感性 甲状腺炎将被用来研究上述物质的潜在相加效应。 关于自身免疫性疾病的化合物。NOD.H2h4动物是一个理想的哨兵 研究遗传和环境潜在相互作用的模型 治疗自身免疫性疾病的药物。

DESCRIPTION (Taken from the Investigator's Abstract) Autoimmune thyroiditis is a multifactorial disease in which genetic predisposition combines with environmental factors to induce disease. In humans, the thyroid can be compromised by diet, drugs, and other synthetic chemicals. Excess iodine may be partially responsible for the increasing prevalence of autoimmune thyroiditis. Other environmental chemicals may also be implicated, but there is little documented evidence as to which chemicals may be involved. Candidate pollutants include polyaromatic hydrocarbons, polybrominated biphenyls, and polychlorinated biphenyls. Infectious agents are also known to trigger autoimmunity. In this proposal the investigators will 1) develop standard reproducible conditions for obtaining a 50% incidence of iodine-exacerbated autoimmune thyroiditis in NOD.H2h4 mice and 2) use this mouse model to study the effects of environmental chemicals in food, industrial products, or infection on development of autoimmune thyroiditis. Methylcholanthrene (MCA) will be used as an example of a polyaromatic hydrocarbon, KBr will be used as an example of a polybrominated biphenyl, and theophylline will be used as an example of a drug which can increase iodine uptake. In Aim 3, lipopolysaccharide (LPS) will be used as a surrogate for infection to determine the role of infectious agents in autoimmune thyroiditis. The genetic predisposition of the NOD.H2h4 mouse to autoimmune thyroiditis will be used to study the potential additive effects of the above compounds on autoimmune disease. The NOD.H2h4 animals are an ideal sentinel model to examine the potential interactions of genetics and environmental agents on autoimmune disease.