Neuropeptide Release Is Impaired in a Mouse Model of Fragile X Mental Retardation Syndrome

Fragile X syndrome (FXS), an inherited disorder characterized by mental retardation and autism-like behaviors, is caused by the failure to transcribe the gene for fragile X mental retardation protein (FMRP), a translational regulator and transporter of select mRNAs. FXS model mice (Find KO mice) exhibit impaired neuropeptide release. Release of biogenic amines does not differ between wild-type (WT) and FmrI KO mice. Rab3A, an mRNA cargo of FMRP involved in the recruitment of vesicles, is decreased by similar to 50% in synaptoneurosomes of FmrI KO mice; however, the number of dense-core vesicles (DCVs) does not differ between WT and FmrI KO mice. Therefore, deficits associated with FXS may reflect this aberrant vesicle release, specifically involving docking and fusion of peptidergic DCVs, and may lead to defective maturation and maintenance of synaptic connections.