Decreased alternative splicing of estrogen receptor-α mRNA in the Alzheimer's disease brain
Decreased alternative splicing of estrogen receptor-α mRNA in the Alzheimer's disease brain
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DOI：
10.1016/j.neurobiolaging.2010.03.010
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发表时间：
2012-02-01
影响因子：
4.2
通讯作者：
Swaab, Dick F.
中科院分区：
文献类型：
--
作者：
Ishunina, Tatjana A.;Swaab, Dick F.
本研究在阿尔茨海默病（Alzheimer’s disease， AD）患者和对照患者的不同脑区中鉴定出62种雌激素受体α (estrogen receptor α, ER α) mRNA剪接变异，并将其分为12组。其中48种剪接形式是首次鉴定。选择性剪接的ER α mrna的分布是脑区域和病例特异性的。显性负缺失（del.）7异构体似乎是主要的剪接变体。与对照组相比，AD病例中每个脑区ER α剪接形式的平均数量较低，尽管在外显子内5‘和3’剪接位点替代使用的大缺失发生率在AD女性病例中更为频繁。del的相对转录水平。7和del。2（缺失的外显子2）变体在AD患者的颞叶皮层中减少，而野生型ER α mRNA的表达没有改变。我们的数据显示，ER α mRNA的选择性剪接在阿尔茨海默病大脑中减少，在阿尔茨海默病女性病例中更为明显。(C) 2012爱思唯尔公司版权所有。
In this study we identified 62 estrogen receptor alpha (ER alpha) mRNA splice variants in different human brain areas of Alzheimer's disease (AD) and control cases and classified them into 12 groups. Forty-eight of these splice forms were identified for the first time. The distribution of alternatively spliced ER alpha mRNAs was brain area-and case-specific. The dominant negative deletion (del.) 7 isoform appeared to be the major splice variant. The average number of ER alpha splice forms per brain area was lower in AD cases compared with controls, although the incidence of large deletions with alternative usage of 5' and 3' splice sites inside exons was more frequent in AD female cases. Relative transcription levels of del. 7 and del. 2 (missing exon 2) variants were decreased in the temporal cortex of AD patients, whereas the expression of the wild type ER alpha mRNA did not change. Our data show that alternative splicing of ER alpha mRNA is diminished in the AD brain and more prominently in AD female cases. (C) 2012 Elsevier Inc. All rights reserved.