In:
Genome Research, Cold Spring Harbor Laboratory, Vol. 12, No. 7 ( 2002-07-01), p. 1029-1039
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. [Sequence data reported in this paper has been deposited in GenBank and assigned the following accession nos: AF517674 , AF517675 , AF517676 , and AF517677 . Supplemental material is available online at http://depts.washington.edu/rhwlab/ and http: www.genome.org . ] The following individuals and institutions kindly provided reagents, samples, or unpublished information as indicated in the paper: K. Matsumoto and the Sir Frederick Banting Research Centre.
Type of Medium:
Online Resource
ISSN:
1088-9051
,
1549-5469
Language:
English
Publisher:
Cold Spring Harbor Laboratory
Publication Date:
2002
detail.hit.zdb_id:
1483456-X
SSG:
12