Faculty Collaboration Database

Lymphopenia in the BB rat model of type 1 diabetes is due to a mutation in a novel immune-associated nucleotide (Ian)-related gene. Genome Res 2002 Jul;12(7):1029-39

Date

07/05/2002

Pubmed ID

12097339

Pubmed Central ID

PMC186618

DOI

10.1101/gr.412702

Scopus ID

2-s2.0-0036062788 (requires institutional sign-in at Scopus site)   195 Citations

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.

Author List

MacMurray AJ, Moralejo DH, Kwitek AE, Rutledge EA, Van Yserloo B, Gohlke P, Speros SJ, Snyder B, Schaefer J, Bieg S, Jiang J, Ettinger RA, Fuller J, Daniels TL, Pettersson A, Orlebeke K, Birren B, Jacob HJ, Lander ES, Lernmark A

Author

Anne E. Kwitek PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Animals
Animals, Congenic
Apoptosis Regulatory Proteins
Diabetes Mellitus, Type 1
Disease Models, Animal
GTP-Binding Proteins
Hematopoietic Stem Cells
Humans
Lymphopenia
Mice
Molecular Sequence Data
Protein Tyrosine Phosphatase, Non-Receptor Type 1
Protein Tyrosine Phosphatase, Non-Receptor Type 22
Protein Tyrosine Phosphatases
Rats
Rats, Inbred BB
Rats, Inbred F344
Rats, Inbred LEC
Rats, Inbred OLETF
Sequence Deletion