Type 1 Diabetes Genes and Pathways Shared by Humans and NOD Mice

J Autoimmun. 2005;25 Suppl:29-33. doi: 10.1016/j.jaut.2005.09.009. Epub 2005 Oct 28.

Abstract

The identification of causative genes for the autoimmune disease type 1 diabetes (T1D) in humans and candidate genes in the NOD mouse has made significant progress in recent years. In addition to sharing structural aspects of the MHC class II molecules that confer susceptibility or resistance to T1D, genes and pathways contributing to autoimmune pathogenesis are held in common by the two species. There are data demonstrating a similar need to establish central tolerance to insulin. Gene variants for the interacting molecules IL2 and CD25, members of a pathway that is essential for immune homeostasis, are present in mice and humans, respectively. Variation of two molecules that negatively regulate T cells, CTLA-4 and the tyrosine phosphatase LYP/PEP, are associated with susceptibility to human and NOD T1D. These observations underscore the value of the NOD mouse model for mechanistic studies on human T1D-associated molecular and cellular pathways.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigens, CD
  • Antigens, Differentiation / genetics
  • CTLA-4 Antigen
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / metabolism*
  • Genetic Predisposition to Disease
  • Humans
  • Interleukin-2 / genetics
  • Mice
  • Mice, Inbred NOD
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22
  • Protein Tyrosine Phosphatases / genetics
  • Receptors, Interleukin-2 / genetics

Substances

  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Ctla4 protein, mouse
  • Interleukin-2
  • Receptors, Interleukin-2
  • PTPN22 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22
  • Protein Tyrosine Phosphatases
  • Ptpn22 protein, mouse