NOD-H2H4 MICE AS A SENTINEL MODEL FOR AUTOIMMUNE THYROID

描述（摘自研究者摘要） 自身免疫性甲状腺炎是一种多因素疾病， 易感性与环境因素结合诱发疾病。 在 人类，甲状腺可以受到饮食，药物和其他合成药物的影响。 化学品 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 但几乎没有证据证明哪些化学物质 可能参与其中。 候选污染物包括多环芳烃， 多溴联苯和多氯联苯。 传染性病原体 也会引发自身免疫 在这项提案中，调查人员 将1）开发标准的可重现条件，以获得50%的发生率 碘加重的自身免疫性甲状腺炎在NOD.H2h4小鼠和2）使用这个 研究食物中环境化学物质影响的小鼠模型， 工业产品，或自身免疫性甲状腺炎的发展感染。 甲基胆蒽（MCA）将用作聚芳族化合物的实例。 烃，KBr将用作多溴联苯的实例， 茶碱将用作可以增加碘的药物的一个例子 摄取。 在目标3中，脂多糖（LPS）将用作以下物质的替代物： 感染，以确定感染因子在自身免疫性疾病中的作用 甲状腺炎 NOD.H2h4小鼠对自身免疫的遗传易感性 甲状腺炎将用于研究上述因素的潜在叠加效应 自身免疫性疾病的药物 NOD.H2h4动物是理想的哨兵 模型来研究遗传和环境的潜在相互作用 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.