Genomic organization and transcript analysis of ICAp69, a target antigen in diabetic autoimmunity

Genomics
R GaedigkH M Dosch

Abstract

Islet cell antigen p69 (ICAp69) is a target self-antigen in autoimmune (insulin-dependent) diabetes mellitus. Distributed over more than 100 kb on chromosome 6 (6{A1-A2}), the single murine genomic locus contains 14 coding exons, 39-271 bp in length. The identified human and mouse intron-exon junctions are identical, with intron sizes ranging from 94 bp to 24 kb and with conserved flanking region intron sequences. cDNA cloning identified alternatively spliced ICAp69 mRNA transcripts. The predominating alpha-transcripts lack exon 4, while beta-transcripts include this exon, which codes translation termination in all reading frames and a truncated molecule following in vitro expression. gamma-Transcripts show splice removal of exons 8-12, while delta-transcripts exclude exon 11. Transcripts use alternative polyadenylation signals including a less frequent ATTAAA sequence. 5'-Untranslated cDNA and genomic sequencing and long PCR analysis suggest the presence of more noncoding exons. All splice variants encode the conserved T-cell epitope (in exon 2) recognized by autoreactive T cells in diabetic children and diabetes-prone NOD mice.

Citations

May 18, 1999·Journal of the National Cancer Institute·C E TuneH M Dosch
Dec 23, 2006·Genome Research·Vikas BansalVineet Bafna
May 17, 2006·Oral Diseases·F CarinciF Pezzetti
Feb 28, 2001·Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-Head and Neck Surgery·T ShpitzerH M Dosch
Nov 30, 2018·Korean journal of family medicine·Nurul Azreen YusofFaridah Mohd Zin
Sep 4, 1999·Journal of Endocrinological Investigation·J M Norris, M Pietropaolo
Oct 18, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·S WinerH M Dosch
Dec 26, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shawn WinerH-Michael Dosch

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