Figure 1. Model for the pathogenesis and correction of FXS.

The mGluR theory of fragile X posits that mGluR5 and FMRP regulate translation of mRNA at the synapse in a functionally opponent manner – mGluR5 activation initiates protein synthesis and FMRP suppresses it. In the absence of FMRP, as is the case in FXS, mGluR5-dependent protein synthesis proceeds unchecked, and consequent excessive translation leads to the diversity of clinical features that make up the syndrome. Our results demonstrate that this progression can be corrected by genetic reduction of mGluR5 activity.