Identification of a major gene responsible for type 1 diabetes in the Komeda diabetes-prone rat.
Type 1 diabetes mellitus is an autoimmune disease involving both environmental and genetic factors. Genetic analyses in humans and rodents have shown that the major histocompatibility complex (MHC) is a major genetic factor and that several other genes may be involved in the development of the disease. We performed genetic analysis of type 1 diabetes in a newly established animal model, the Komeda diabetes-prone (KDP) rat, and found that most of the genetic predisposition to diabetes is accounted for by two major susceptibility genes, MHC and Iddm/kdp1. In addition, we identified a nonsense mutation in the Casitas B-lineage lymphoma b (Cblb) gene by positional cloning of Iddm/kdp1. In this paper, I review our positional cloning analysis of Iddm/kdp1 and propose a two-gene model of the development of type 1 diabetes in which two major susceptibility genes, Cblb and MHC, determine autoimmune reaction and tissue specificity to pancreatic beta-cells, respectively.
Yokoi
Norihide
N
Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Japan.
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D015551:Autoimmunity / Q000235:genetics; D003001:Cloning, Molecular / Q000379:methods; D018389:Codon, Nonsense; D003922:Diabetes Mellitus, Type 1; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000235:genetics*; D009154:Mutation; D050721:Proto-Oncogene Proteins c-cbl; D051381:Rats; D011919:Rats, Inbred Strains; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; C492213:Cblb protein, rat; D018389:Codon, Nonsense; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases