GENOMIC ORGANIZATION AND TRANSCRIPT ANALYSIS OF ICAP69, A TARGET ANTIGEN IN DIABETIC AUTOIMMUNITY

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 contai ns 14 coding exons, 39-271 bp in length. The identified human and mous e intron-exon junctions are identical, with intron sizes ranging from 94 bp to 24 kb and with conserved flanking region intron sequences. cD NA cloning identified alternatively spliced ICAp69 mRNA transcripts, T he 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 ge nomic sequencing and long PCR analysis suggest the presence of more no ncoding exons. All splice variants encode the conserved T-cell epitope (in exon 2) recognized by autoreactive T cells in diabetic children a nd diabetes-prone NOD mice. (C) 1996 Academic Press, Inc.