Levy-Lahad E, Poorkaj P, Wang K, Fu Y H, Oshima J, Mulligan J, Schellenberg G D
Division of Medical Genetics, University of Washington, Seattle, Washington, 98195, USA.
Genomics. 1996 Jun 1;34(2):198-204. doi: 10.1006/geno.1996.0266.
Mutations in the gene STM2 result in autosomal dominant familial Alzheimer disease. To screen for mutations and to identify regulatory elements for this gene, the genomic DNA sequence and intron-exon structure were determined. Twelve exons including 10 coding exons were identified in a genomic region spanning 23,737 bp. The first 2 exons encode the 5'-untranslated region. Expression analysis of STM2 indicates that two transcripts of 2.4 and 2.8 kb are found in skeletal muscle, pancreas, and heart. In addition, a splice variant of the 2.4-kb transcript was identified that is the result of the use of an alternative splice acceptor site located in exon 10. The use of this site results in a transcript lacking a single glutamate. The promotor for this gene and the alternatively spliced exons leading to the 2.8-kb form of the gene remain to be identified. Expression of STM2 was high in skeletal muscle and pancreas, with comparatively low levels observed in brain. This expression pattern is intriguing since in Alzheimer disease, pathology and degeneration are observed only in the central nervous system.
STM2基因的突变会导致常染色体显性遗传性家族性阿尔茨海默病。为了筛查该基因的突变并鉴定其调控元件，我们测定了其基因组DNA序列和内含子-外显子结构。在一个跨度为23737 bp的基因组区域中鉴定出了12个外显子，其中包括10个编码外显子。前两个外显子编码5'-非翻译区。STM2的表达分析表明，在骨骼肌、胰腺和心脏中发现了2.4 kb和2.8 kb的两种转录本。此外，还鉴定出了2.4 kb转录本的一种剪接变体，它是使用位于外显子10中的一个替代剪接受体位点的结果。使用这个位点会导致转录本缺少一个谷氨酸。该基因的启动子以及导致该基因2.8 kb形式的可变剪接外显子仍有待确定。STM2在骨骼肌和胰腺中的表达较高，而在大脑中观察到的水平相对较低。这种表达模式很有趣，因为在阿尔茨海默病中，病理变化和神经退行性变仅在中枢神经系统中观察到。
