NOD-H2H4 Mice as a Sentinel Model for Autoimmune Thyroid

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.