EXPRESSION OF 4 ALTERNATIVE DYSTROPHIN TRANSCRIPTS IN BRAIN-REGIONS REGULATED BY DIFFERENT PROMOTERS
EXPRESSION OF 4 ALTERNATIVE DYSTROPHIN TRANSCRIPTS IN BRAIN-REGIONS REGULATED BY DIFFERENT PROMOTERS
复制标题
DOI：
10.1093/hmg/1.7.505
复制
发表时间：
1992-10-01
影响因子：
3.5
通讯作者：
BARNARD, PJ
中科院分区：
文献类型：
--
作者：
GORECKI, DC;MONACO, AP;BARNARD, PJ
三分之一的杜氏肌营养不良症患者会出现认知障碍，杜氏肌营养不良症是一种致命的X连锁隐性疾病，由脑和肌肉中表达的肌营养不良蛋白基因突变引起，这两种转录物具有交替的第一外显子。以前的报道表明，'脑型'肌营养不良蛋白转录占主导地位的大脑。使用原位杂交与反义寡核苷酸，在特定的大脑区域的四个不同的mRNA的表达在这里证明，14 kb的肌肉型和脑型转录被发现共存于皮层和海马神经元和两个新的转录已被确定在齿状回和小脑浦肯野神经元，分别。后者有一个新的第一外显子，从小鼠和人类中分离和测序，并编码一种蛋白质，其氨基末端与已知的肌肉和脑型同种型不同。在人类中定位此外显子在肌肉型启动子和肌营养不良蛋白基因的第二外显子之间的大内含子中。这一发现的四个不同的启动子调控的替代转录在大脑中揭示了一个新的复杂性，肌营养不良蛋白的表达，可能有重要的见解精神发育迟滞的机制。
Cognitive impairment occurs in one-third of patients with Duchenne muscular dystrophy, a lethal X-linked, recessive disease caused by mutations in the dystrophin gene which is expressed in both brain and muscle, the two transcripts having alternative first exons. Previous reports have indicated that the 'brain-type' dystrophin transcript predominates in brain. Using in situ hybridisation with antisense oligonucleotides, expression of four distinct mRNAs in specific brain areas is demonstrated here; the 14 kb muscle-type and brain-type transcripts were found to coexist in cortical and hippocampal neurons and two new transcripts have been identified in dentate gyrus and cerebellar Purkinje neurons, respectively. The latter has a novel first exon which was isolated and sequenced from mouse and human, and which would encode a protein with a different amino-terminus from the known muscle- and brain-type isoforms. Mapping in human located this exon in a large intron between the muscle-type promoter and second exon of the dystrophin gene. This finding of four alternative transcripts regulated by different promoters in brain reveals a new complexity to dystrophin expression that may have important insights for mental retardation mechanisms.