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PMID: 8326004 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Islet cell autoantigen 69 kD (ICA69). Molecular cloning and characterization of a novel diabetes-associated autoantigen.

The Journal of clinical investigation ·Vol. 92 ·No. 1 ·1993-07-00 ·Pages 359-71

Pietropaolo M, Castaño L, Babu S, Buelow R, Kuo YL, Martin S, Martin A, Powers AC, Prochazka M, Naggert J

Abstract

We have identified a novel 69-kD peptide autoantigen (ICA69) associated with insulin-dependent diabetes mellitus (IDDM) by screening a human islet lambda gt11 cDNA expression library with cytoplasmic islet cell antibody positive sera from relatives of IDDM patients who progressed to the overt disease. The deduced open reading frame of the ICA69 cDNA predicts a 483-amino acid protein. ICA69 shows no nucleotide or amino acid sequence relation to any known sequence in GenBank, except for two short regions of similarity with BSA. The ICA69 cDNA probe hybridizes with a 2-kb mRNA in poly(A+) RNA from human pancreas, brain, heart, thyroid, and kidney, but not with skeletal muscle, placenta, spleen, or ovary. Expression of ICA69 was also detected in beta cells and cell lines, as well as in tumoral tissue of islet cell origin. The native ICA69 molecule migrates to 69 kD in SDS-PAGE as detected with specific antibodies. Serum samples from relatives of IDDM patients specifically reacted with affinity-purified recombinant ICA69 on Western blotting. The structural gene for ICA69 was designated ICA1. A homologue in the mouse, designated Ica-1 was mapped to the proximal end of chromosome 6 (within 6 cM of the Met protooncogene). ICA69 adds a novel autoantigen to the family of identified islet target molecules, and by the manner of its identification and characterization large amounts of antigen are available for development of quantitative, convenient predictive assays for autoantibodies and analysis of the role of this molecule in diabetes autoimmunity, as well as its physiologic function.

Related Genes
ICA69 Ica-1 Met
MeSH Terms
Amino Acid Sequence Animals Autoantigens/chemistry,genetics Base Sequence Chromosome Mapping Cloning, Molecular Cricetinae DNA/genetics Diabetes Mellitus, Type 1/immunology Gene Expression Genetic Linkage Humans Immunoenzyme Techniques Islets of Langerhans/immunology Mice Molecular Sequence Data Molecular Weight Oligodeoxyribonucleotides/chemistry RNA, Messenger/genetics Rats Recombinant Proteins/genetics,immunology Sequence Alignment Sequence Homology, Amino Acid Transfection
Chemicals
Autoantigens Oligodeoxyribonucleotides RNA, Messenger Recombinant Proteins DNA
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Pietropaolo M
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Science Center, Denver 80262.
Castaño L
Babu S
Buelow R
Kuo Y L
Martin S
Martin A
Powers A C
Prochazka M
Naggert J
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI116574
Published
1993-07-00
Pages
359-71
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC293615
Subset
IM
Grants
NIDDK NIH HHS · DK 27722 · United States
NIDDK NIH HHS · DK 32083 · United States
NIDDK NIH HHS · DK 36175 · United States
Databases
GENBANK
L01100
External Links
PubMed source DOI: 10.1172/JCI116574 PMC Full Text View journal details
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