Immunopathogenesis Of The Nod Mouse

The NOD mouse model of type 1A (immune-mediated) diabetes and genetic derivatives of this strain are probably the most extensively studied autoimmune animal models (1–4  ). NOD mice spontaneously develop insulitis. This is followed in the great majority of female mice by sufficient beta-cell destruction to result in overt diabetes and approximately 50% of male mice develop diabetes. Insulitis develops between 4 and 8 weeks and over a prolonged period of time increasing numbers of mice develop severe hyperglycemia. In addition, the mice develop sialitis and other autoimmune disorders, such as thyroiditis, retinitis, and autoimmune neuropathy, depending upon the genetic backgrounds (5–7  ). Multiple derivatives of the NOD model (congenic strains of mice with specific mutations and transgenes) are available from repositories at the Jackson Laboratories and Taconic and from individual investigators. There is no doubt that type 1A diabetes is the result of T cell-mediated destruction of beta cells with genetic mutations and therapies that eliminate (e.g., Rag and SCID mutations) T cells preventing disease and ability to transfer the disease with autoreactive T cells.