Lymphopenia in the BB Rat Model of Type 1 Diabetes is Due to a Mutation in a Novel Immune-associated Nucleotide (Ian)-related Gene

Overview

Journal Genome Res

Specialty Genetics

Date 2002 Jul 5

PMID 12097339

Citations 94

Authors

Armand J Macmurray

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

Affiliations

Soon will be listed here.

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.

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