Genomic structure and expression of STM2, the chromosome 1 familial Alzheimer disease gene.
Genomic structure and expression of STM2, the chromosome 1 familial Alzheimer disease gene.
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STM2（1 号染色体家族性阿尔茨海默病基因）的基因组结构和表达。
DOI：
10.1006/geno.1996.0266
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发表时间：
1996
期刊：
影响因子：
4.4
通讯作者：
Schellenberg,GD
中科院分区：
文献类型：
--
作者：
Levy-Lahad,E;Poorkaj,P;Wang,K;Fu,YH;Oshima,J;Mulligan,J;Schellenberg,GD
STM 2基因突变导致常染色体显性遗传家族性阿尔茨海默病。为了筛选突变并鉴定该基因的调控元件，测定了基因组DNA序列和内含子-外显子结构。在23，737 bp的基因组区域中鉴定了12个外显子，包括10个编码外显子。前2个外显子编码5′-非翻译区。STM 2的表达分析表明，在骨骼肌、胰腺和心脏中发现了2.4和2.8 kb的两种转录物。此外，2.4 kb转录本的剪接变体被鉴定为使用位于外显子10中的选择性剪接受体位点的结果。该位点的使用导致缺少单个谷氨酸的转录物。该基因的启动子和导致2.8 kb基因形式的可变剪接外显子仍有待鉴定。STM 2在骨骼肌和胰腺中表达较高，在脑中观察到相对较低的水平。这种表达模式是有趣的，因为在阿尔茨海默病中，病理和变性仅在中枢神经系统中观察到。
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.