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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Identification of a major gene responsible for type 1 diabetes in the Komeda diabetes-prone rat. 1589 18

The Komeda diabetes-prone (KDP) rat is an animal model of human autoimmune type 1 diabetes. We have previously shown that two major susceptibility genes, the major histocompatibility complex (MHC) RT1(u) haplotype and Cblb (Casitas B-lineage lymphoma b) mutation, are responsible for the development of diabetes in KDP rats, suggesting a two-gene model for development of the disease. To confirm the two-gene model, we produced a congenic strain carrying mutated Cblb alleles of the KDP rat on a non-KDP genetic background harboring the RT1(u) haplotype on its MHC. Despite the low incidence and delayed onset of diabetes, the congenic strain did develop the disease, indicating that type 1 diabetes can be reconstituted on a non-KDP genetic background with the RT1(u) haplotype and Cblb mutation. Similar to observations in KDP rats, the congenic strain showed insulitis and thyroiditis, symptoms of autoimmunity. The low incidence and delayed onset of the disease strongly suggest involvement of genetic modifiers; the congenic strain established in this study should be useful for the mapping and identification of such modifiers.
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PMID:Genetic reconstitution of autoimmune type 1 diabetes with two major susceptibility genes in the rat. 1725 98

Casitas B-lineage lymphoma b (Cblb) is a negative regulator of T-cell activation and dysfunction of Cblb in rats and mice results in autoimmunity. In particular, a nonsense mutation in Cblb has been identified in a rat model of autoimmune type 1 diabetes. To clarify the possible involvement of CBLB mutation in type 1 diabetes in humans, we performed mutation screening of CBLB and characterized functional properties of the mutations in Japanese subjects. Six missense mutations (A155V, F328L, N466D, K837R, T882A, and R968L) were identified in one diabetic subject each, excepting N466D. Of these mutations, F328L showed impaired suppression of T-cell activation and was a loss-of-function mutation. These data suggest that the F328L mutation is involved in the development of autoimmune diseases including type 1 diabetes, and also provide insight into the structure-function relationship of CBLB protein.
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PMID:Identification and functional analysis of CBLB mutations in type 1 diabetes. 1820 52