Previous studies by other research groups had shown that many mRNAs are bound by FMRP, and many protein levels are altered—and that the vast majority of these proteins are produced in excess in Fragile X. Using new methods, these investigators determined which messenger RNAs are bound most tightly to FMRP, and how the production of the proteins encoded by those mRNAs is altered in Fragile X.
Recently this team discovered that one mRNA is bound more strongly than all others, and the protein product of that mRNA is greatly reduced in Fragile X. The Fragile X protein (FMRP) regulates production of the critical enzyme DgkK, a critical regulatory enzyme involved in multiple signaling pathways, so the deficiency of this one protein could explain many of the different abnormalities observed in Fragile X. Most importantly, there are available drugs which can increase production of DgkK, and this project will test them in the Fragile X mouse model.