The mGluR5 antagonist AFQ056 does not affect methylation and transcription of the mutant <it>FMR1 </it>gene <it>in vitro</it>

• Main Authors: Tabolacci Elisabetta (Author), Pirozzi Filomena (Author), Gomez-Mancilla Baltazar (Author), Gasparini Fabrizio (Author), Neri Giovanni (Author)
• Format: Book
• Published: BMC, 2012-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<p>Abstract</p> <p>Background</p> <p>Fragile X syndrome (FXS), the leading cause of inherited mental retardation, is due to expansion and methylation of a CGG sequence in the <it>FMR1 </it>gene, which result in its silencing and consequent absence of FMRP protein. This absence causes loss of repression of metabotropic glutamate receptor 5 (mGluR5)-mediated pathways resulting in the behavioral and cognitive impairments associated with FXS. In a randomized, double-blind trial it was recently demonstrated a beneficial effect of AFQ056, a selective inhibitor of metabotrobic glutamate receptor type 5 (mGluR5), on fully methylated FXS patients respect to partially methylated FXS ones.</p> <p>Methods</p> <p>To determine whether AFQ056 may have secondary effects on the methylation and transcription of <it>FMR1</it>, here we treated three FXS lymphoblastoid cell lines and one normal control male line. A quantitative RT-PCR was performed to assess transcriptional reactivation of the <it>FMR1 </it>gene. To assess the methylation status of the <it>FMR1 </it>gene promoter it was carried out a bisulphite sequencing analysis.</p> <p>Results</p> <p>Both <it>FMR1</it>-mRNA levels and DNA methylation were unmodified with respect to untreated controls.</p> <p>Conclusions</p> <p>These results demonstrate that the AFQ056 effect on fully methylated FXS patients is not due to a secondary effect on DNA methylation and consequent transcriptional activation of <it>FMR1</it>.</p>

Item Description

10.1186/1471-2350-13-13
1471-2350