Clonal Rett Syndrome cell lines to test compounds for activation of wild-type MeCP2 expression

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:21

Article

Yu, Dongbo¹  Sakurai, Fuminori²  Corey, David R.¹ 

[1] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA

[2] Osaka Univ, Grad Sch Pharmaceut Sci, Dept Biochem & Mol Biol, Suita, Osaka 5650871, Japan

关键词: Rett Syndrome;    Reversal of X-inactivation;    Allele-specific cell-line;    MeCP2;    Nested PCR;   

DOI  :  10.1016/j.bmcl.2011.07.053

来源: Elsevier

【 摘 要 】

Rett Syndrome is an X-linked progressive neurological disorder caused by inactivation of one allele of the MECP2 gene. There are no curative treatments, and activation of wild-type MECP2 expression is one strategy for stabilizing or reversing the disease. We isolated fibroblast clones that express exclusively either the wild-type or a 32-bp-deletion mutant form of MECP2. We developed a sensitive assay for measuring wild-type MECP2 mRNA levels and tested small molecule epigenetic activators for their ability to activate gene expression. Although our pilot screen did not identify activators of MECP2 expression, it established the value of using clonal cells and defined challenges that must be overcome. (C) 2011 Elsevier Ltd. All rights reserved.

【 授权许可】

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