Gaedigk R, Karges W, Hui M F, Scherer S W, Dosch H M
Department of Pediatrics and Immunology, University of Toronto, Toronto, Ontario, M5G 1X8, Canada.
Genomics. 1996 Dec 15;38(3):382-91. doi: 10.1006/geno.1996.0641.
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.
胰岛细胞抗原p69（ICAp69）是自身免疫性（胰岛素依赖型）糖尿病中的一种靶自身抗原。该单一的小鼠基因组位点分布在6号染色体（6{A1 - A2}）上超过100 kb的区域，包含14个编码外显子，长度为39 - 271 bp。已确定的人和小鼠内含子 - 外显子连接是相同的，内含子大小范围从94 bp到24 kb，且内含子侧翼区域序列保守。cDNA克隆鉴定出了可变剪接的ICAp69 mRNA转录本。占主导的α转录本缺少外显子4，而β转录本包含该外显子，其在所有阅读框中编码翻译终止，并且在体外表达后产生截短分子。γ转录本显示外显子8 - 12的剪接去除，而δ转录本排除外显子11。转录本使用包括较少出现的ATTAAA序列在内的可变聚腺苷酸化信号。5' - 非翻译cDNA和基因组测序以及长PCR分析表明存在更多非编码外显子。所有剪接变体均编码糖尿病儿童和易患糖尿病的非肥胖糖尿病（NOD）小鼠中自身反应性T细胞识别的保守T细胞表位（在外显子2中）。
