| Literature DB >> 12097339 |
Armand J MacMurray1, Daniel H Moralejo, Anne E Kwitek, Elizabeth A Rutledge, Brian Van Yserloo, Paul Gohlke, Sara J Speros, Ben Snyder, Jonathan Schaefer, Sabine Bieg, Jianjie Jiang, Ruth A Ettinger, Jessica Fuller, Terri L Daniels, Anna Pettersson, Kimberly Orlebeke, Bruce Birren, Howard J Jacob, Eric S Lander, Ake Lernmark.
Abstract
The BB (BioBreeding) rat is one of the best models of spontaneous autoimmune diabetes and is used to study non-MHC loci contributing to Type 1 diabetes. Type 1 diabetes in the diabetes-prone BB (BBDP) rat is polygenic, dependent upon mutations at several loci. Iddm1, on chromosome 4, is responsible for a lymphopenia (lyp) phenotype and is essential to diabetes. In this study, we report the positional cloning of the Iddm1/lyp locus. We show that lymphopenia is due to a frameshift deletion in a novel member (Ian5) of the Immune-Associated Nucleotide (IAN)-related gene family, resulting in truncation of a significant portion of the protein. This mutation was absent in 37 other inbred rat strains that are nonlymphopenic and nondiabetic. The IAN gene family, lying within a tight cluster on rat chromosome 4, mouse chromosome 6, and human chromosome 7, is poorly characterized. Some members of the family have been shown to be expressed in mature T cells and switched on during thymic T-cell development, suggesting that Ian5 may be a key factor in T-cell development. The lymphopenia mutation may thus be useful not only to elucidate Type 1 diabetes, but also in the function of the Ian gene family as a whole.Entities:
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Year: 2002 PMID： 12097339 PMCID： PMC186618 DOI： 10.1101/gr.412702
Source DB: PubMed Journal: Genome Res ISSN： 1088-9051 Impact factor: 9.043