Linked Life Data

11289059

Source:http://linkedlifedata.com/resource/pubmed/id/11289059

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2001-4-5
pubmed:abstractText
Type 1 diabetes results from the autoimmune destruction of pancreatic beta-cells in genetically susceptible individuals. Growing evidence suggests that genetically determined variation in the expression of self-antigens in thymus may affect the shaping of the T-cell repertoire and susceptibility to autoimmunity. For example, both allelic variation and parent-of-origin effects influence the thymic expression of insulin (a known type 1 diabetes autoantigen), and insulin gene transcription levels in thymus inversely correlate with susceptibility in both humans and transgenic models. It is unclear why patients lose tolerance to IA-2 (insulinoma-associated tyrosine phosphatase-like protein, or islet cell antigen 512 [ICA512]), especially because IA-2 polymorphisms are not associated with type 1 diabetes. We report that alternative splicing determines differential IA-2 expression in islets compared with thymus and spleen. Islets express full-length mRNA and two alternatively spliced transcripts, whereas thymus and spleen exclusively express an alternatively spliced transcript lacking exon 13. This encodes for the transmembrane (TM) and juxta-membrane (JM) domains that comprise several type 1 diabetes target epitopes, supporting the concept that tolerance to IA-2 epitopes not expressed in lymphoid organs may not be achieved. We propose differential splicing as a regulatory mechanism of gene expression playing a permissive role in the development of autoimmune responses to IA-2. Our findings also show that candidate gene expression studies can help in dissecting the complex genetic determinants of a multifactorial disease such as type 1 diabetes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
895-900
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11289059-Adult, pubmed-meshheading:11289059-Amino Acid Sequence, pubmed-meshheading:11289059-Autoantigens, pubmed-meshheading:11289059-Autoimmunity, pubmed-meshheading:11289059-Base Sequence, pubmed-meshheading:11289059-Diabetes Mellitus, Type 1, pubmed-meshheading:11289059-Female, pubmed-meshheading:11289059-Fetus, pubmed-meshheading:11289059-Humans, pubmed-meshheading:11289059-Infant, pubmed-meshheading:11289059-Infant, Newborn, pubmed-meshheading:11289059-Lymphoid Tissue, pubmed-meshheading:11289059-Male, pubmed-meshheading:11289059-Membrane Proteins, pubmed-meshheading:11289059-Middle Aged, pubmed-meshheading:11289059-Molecular Sequence Data, pubmed-meshheading:11289059-Pancreas, pubmed-meshheading:11289059-Protein Tyrosine Phosphatase, Non-Receptor Type 1, pubmed-meshheading:11289059-Protein Tyrosine Phosphatases, pubmed-meshheading:11289059-RNA Splicing, pubmed-meshheading:11289059-Receptor-Like Protein Tyrosine Phosphatases, Class 8
pubmed:year
2001
pubmed:articleTitle
Differential splicing of the IA-2 mRNA in pancreas and lymphoid organs as a permissive genetic mechanism for autoimmunity against the IA-2 type 1 diabetes autoantigen.
pubmed:affiliation
Immunogenetics Program and the Diabetes Research Institute, University of Miami, Florida 33136, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't