Type 1 diabetes genes and pathways shared by humans and NOD mice.
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.
Wicker
Linda S
LS
Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, University of Cambridge, Cambridge Institute for Medical Research, Cambridge CB2 2XY, UK. linda.wicker@cimr.cam.ac.uk
Clark
Jan
J
Fraser
Heather I
HI
Garner
Valerie E S
VE
Gonzalez-Munoz
Andrea
A
Healy
Barry
B
Howlett
Sarah
S
Hunter
Kara
K
Rainbow
Dan
D
Rosa
Raymond L
RL
Smink
Luc J
LJ
Todd
John A
JA
Peterson
Laurence B
LB
D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics; D060908:CTLA-4 Antigen; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000235:genetics
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; C516765:PTPN22 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases; C516766:Ptpn22 protein, mouse