The GABA A Receptor is an FMRP Target with Therapeutic Potential in Fragile X Syndrome

However, the molecular mechanism underlying GABA A ergic deficits has remained largely unknown. Here, we demonstrate reduced mRNA expression of GABA A receptor subunits in the cortex and cerebellum of young Fmr1 knockout mice.

In addition, we show that the previously reported underexpression of specific subunits of the GABA A receptor can be corrected in YAC transgenic rescue mice, containing the full-length human FMR1 gene in an Fmr1 knockout background. Moreover, we demonstrate that FMRP directly binds several GABA A receptor mRNAs. Finally, positive allosteric modulation of GABA A receptors with the neurosteroid ganaxolone can modulate specific behaviours in Fmr1 knockout mice, emphasizing the therapeutic potential of the receptor.