論文 - 詳細
| RRC ID | 36 |
|---|---|
| 著者 | Yokoi N, Komeda K, Wang HY, Yano H, Kitada K, Saitoh Y, Seino Y, Yasuda K, Serikawa T, Seino S. |
| タイトル | Cblb is a major susceptibility gene for rat type 1 diabetes mellitus. |
| ジャーナル | Nat Genet |
| Abstract |
The autoimmune disease type 1 diabetes mellitus (insulin-dependent diabetes mellitus, IDDM) has a multifactorial etiology. So far, the major histocompatibility complex (MHC) is the only major susceptibility locus that has been identified for this disease and its animal models. The Komeda diabetes-prone (KDP) rat is a spontaneous animal model of human type 1 diabetes in which the major susceptibility locus Iddm/kdp1 accounts, in combination with MHC, for most of the genetic predisposition to diabetes. Here we report the positional cloning of Iddm/kdp1 and identify a nonsense mutation in Cblb, a member of the Cbl/Sli family of ubiquitin-protein ligases. Lymphocytes of the KDP rat infiltrate into pancreatic islets and several tissues including thyroid gland and kidney, indicating autoimmunity. Similar findings in Cblb-deficient mice are caused by enhanced T-cell activation. Transgenic complementation with wildtype Cblb significantly suppresses development of the KDP phenotype. Thus, Cblb functions as a negative regulator of autoimmunity and Cblb is a major susceptibility gene for type 1 diabetes in the rat. Impairment of the Cblb signaling pathway may contribute to human autoimmune diseases, including type 1 diabetes. |
| 巻・号 | 31(4) |
| ページ | 391-4 |
| 公開日 | 2002-8-1 |
| DOI | 10.1038/ng927 |
| PII | ng927 |
| PMID | 12118252 |
| MeSH | Activated-Leukocyte Cell Adhesion Molecule / genetics Adaptor Proteins, Signal Transducing* Animals Animals, Genetically Modified Autoimmunity / genetics Chromosome Mapping Cloning, Molecular Diabetes Mellitus, Type 1 / genetics* Diabetes Mellitus, Type 1 / pathology Female Genetic Predisposition to Disease Heterozygote Ligases / genetics* Ligases / metabolism* Lymphocyte Activation Male Mice Molecular Sequence Data Mutation Proto-Oncogene Proteins c-cbl Rats Rats, Mutant Strains Rats, Sprague-Dawley T-Lymphocytes / metabolism T-Lymphocytes / pathology Ubiquitin-Protein Ligases* |
| IF | 27.605 |
| 引用数 | 144 |
| WOS 分野 | GENETICS & HEREDITY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ラット | KDP/Tky(strainID=15) TM/Kyo(strainID=10) |