Direct evidence for the contribution of the unique I-ANOD to the development of insulitis in non-obese diabetic mice

Nature. 1990 Jun 21;345(6277):722-4. doi: 10.1038/345722a0.


Insulin-dependent diabetes mellitus is characterized by the infiltration of lymphocytes into the islets of Langerhans of the pancreas (insulitis) followed by destruction of insulin-secreting beta-cells leading to overt diabetes. The best model for the disease is the non-obese diabetic (NOD) mouse. Two unusual features of the class II major histocompatibility complex (MHC) of the NOD mouse are the absence of I-E and the presence of unique I-A molecules (I-ANOD), in which aspartic acid at position 57 of the beta-chain is replaced by serine. This feature is also found in the HLA-DQ chain of many Caucasians with insulin-dependent diabetes mellitus. We have previously reported that the expression of I-E prevents the development of insulitis in NOD mouse. Here we report that the expression of I-Ak (A alpha kA beta k) in transgenic NOD mice can also prevent insulitis, and that this protection is seen not only when the I-A beta-chain has aspartic acid as residue 57, but also when this residue is serine. These results show that the single amino-acid substitution at position 57 of the I-A beta-chain from aspartic acid to serine is not sufficient for the development of the disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aspartic Acid
  • Base Sequence
  • Diabetes Mellitus, Experimental / immunology*
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • Gene Expression
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / immunology*
  • Islets of Langerhans / immunology
  • Islets of Langerhans / pathology*
  • Lymphocytes / pathology*
  • Male
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Mutation
  • Nucleic Acid Hybridization
  • Oligonucleotide Probes
  • Protein Conformation
  • Serine


  • Histocompatibility Antigens Class II
  • I-E-antigen
  • Oligonucleotide Probes
  • Aspartic Acid
  • Serine