Journal article
Analysis of the rat Iddm14 diabetes susceptibility locus in multiple rat strains: identification of a susceptibility haplotype in the Tcrb-V locus
Mammalian genome, v 20(3), pp 162-169
Mar 2009
PMID: 19205800
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Iddm14
(formerly
Iddm4
) is a non-MHC-linked genetic locus associated with autoimmune diabetes. Its effects have been well-documented in BB-derived rats in which diabetes is either induced by immunologic perturbation or occurs spontaneously. The role of
Iddm14
in non-BB rat strains is unknown. Our goal was to extend the analysis of
Iddm14
in new diabetes-susceptible strains and to identify candidate genes in the rat
Iddm14
diabetes susceptibility locus that are common to these multiple diabetic strains. To determine if
Iddm14
is important in strains other than BB, we first genotyped a (LEW.1WR1 × WF)F2 cohort in which diabetes was induced by perturbation with polyinosinic:polycytidylic acid. We found that
Iddm14
is a major determinant of diabetes susceptibility in LEW.1WR1 rats. We then used nucleotide sequencing to establish a strain distribution pattern of polymorphisms (insertions, deletions, and single nucleotide polymorphisms [SNPs]) that predicts susceptibility to diabetes in a panel of inbred and congenic rats. Using the positional information from the congenic strains and the new linkage data, we identified a susceptibility haplotype in the T-cell receptor V
β
chain (
Tcrb-V
) locus. This haplotype includes
Tcrb-V13
, which is identical in five susceptible strains but different in resistant WF and F344 rats. We conclude that
Iddm14
is a powerful determinant of both spontaneous and induced autoimmune diabetes in multiple rat strains, and that
Tcrb-V13
SNPs constitute a haplotype of gene elements that may be critical for autoimmune diabetes in rats.
Metrics
Details
- Title
- Analysis of the rat Iddm14 diabetes susceptibility locus in multiple rat strains: identification of a susceptibility haplotype in the Tcrb-V locus
- Creators
- John P Mordes - Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USALaura Cort - Department of Microbiology and Immunology, Center for Immunogenetics and Inflammatory Diseases, Drexel University College of Medicine, Philadelphia, PA 19129, USAElaine Norowski - Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USAJean Leif - Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USAJessica M Fuller - Department of Medicine, University of Washington, Seattle, WA 98195, USA. Department of Clinical Sciences (Malmö), Clinical Research Center, Lund University, Malmö, SwedenÅke Lernmark - Department of Medicine, University of Washington, Seattle, WA 98195, USA. Department of Clinical Sciences (Malmö), Clinical Research Center, Lund University, Malmö, SwedenDale L Greiner - Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USAElizabeth P Blankenhorn - Department of Microbiology and Immunology, Center for Immunogenetics and Inflammatory Diseases, Drexel University College of Medicine, Philadelphia, PA 19129, USA
- Publication Details
- Mammalian genome, v 20(3), pp 162-169
- Publisher
- Springer Nature
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology; [Retired Faculty]
- Web of Science ID
- WOS:000264486300004
- Scopus ID
- 2-s2.0-62749169934
- Other Identifier
- 991014878241904721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Biotechnology & Applied Microbiology
- Genetics & Heredity