RT Journal
A1 MacMurray, Armand J.
A1 Moralejo, Daniel H.
A1 Kwitek, Anne E.
A1 Rutledge, Elizabeth A.
A1 Van Yserloo, Brian
A1 Gohlke, Paul
A1 Speros, Sara J.
A1 Snyder, Ben
A1 Schaefer, Jonathan
A1 Bieg, Sabine
A1 Jiang, Jianjie
A1 Ettinger, Ruth A.
A1 Fuller, Jessica
A1 Daniels, Terri L.
A1 Pettersson, Anna
A1 Orlebeke, Kimberly
A1 Birren, Bruce
A1 Jacob, Howard J.
A1 Lander, Eric S.
A1 Lernmark, Åke
T1 Lymphopenia in the BB Rat Model of Type 1 Diabetes is Due to a Mutation in a Novel Immune-Associated Nucleotide (Ian)-Related Gene
JF Genome Research 
JO Genome Research 
YR 2002 
FD July 01 
VO 12 
IS 7 
SP 1029 
OP 1039 
DO 10.1101/gr.412702 
UL http://genome.cshlp.org/content/12/7/1029.abstract 
AB 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 theIddm1/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 thatIan5 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 ] The following individuals and institutions kindly provided reagents, samples, or unpublished information as indicated in the paper: K. Matsumoto and the Sir Frederick Banting Research Centre.