The Effect of MHC Encoding Transgenes on IDDM in NOD Mice

The nonobese diabetic (NOD) mouse provides an excellent animal model (1) of insulin-dependent diabetes mellitus (IDDM), an autoimmune disease in which the β cells of the pancreas are selectively and specifically destroyed by cells of the immune system. The spontaneous development of IDDM in NOD mice has been shown to be under polygenic control with major histocompatibility complex (MHC)-encoded genes playing a major role (2, 3). The MHC class II of the NOD consists of AαdAβg7 and EαbEβg7 heterodimers, thus resulting in the lack of expression of I-E in NOD mice (2) The Aβ chain of NOD mice contains several unusual amino acids in the first external domain including a serine at position 57 and a histidine at position 56 where most other mouse strains have an aspartate and a proline, respectively (4). Interest in the amino acid usage at position 57 stemmed largely from genetic studies of IDDM in humans, where it was observed that individuals protected from disease development tend to have a charged residue at this position in their DQβ chain (5). By analogy, therefore, it was proposed that serine 57 in NODAβg7 may predispose to development of IDDM in this strain.