FMR1 and fragile X syndrome: The seminal investigation of the eCB system in different animal models of FXS (Maccarrone et al., 2010b) has provided evidence that in mice lacking both the FMR1-encoding FXS protein FMRP (FMRP KO mice) and the regulatory brain cytoplasmic 1 RNA (BC1 KO mice) there is a severe alteration of the functional coupling between metabotropic glutamate 5 receptors (mGlu5Rs) and eCB signaling.