Localization of the fragile X mental retardation 2 (FMR2) protein in mammalian brain

The transcriptional silencing of the FMR2 gene has been implicated in FRAXE mental retardation. FRAXE individuals have been shown to exhibit learning deficits, including speech delay, reading and writing problems. FMR2 encode s a large protein of 1311 amino acids and is a member of a gene family enco ding proline-serine-rich proteins that have properties of nuclear transcrip tion factors. To characterize the expression of the fragile X mental retard ation 2 (FMR2) protein, polyclonal antibodies were raised against two regio ns of the human FMR2 protein and used in immunofluorescence experiments on mouse brain cryosections. Our results demonstrate for the first time that t he FMR2 protein is localized in neurons of the neocortex, Purkinje cells of the cerebellum and the granule cell layer of the hippocampus. FMR2 stainin g is shown to colocalize with the nuclear stain 4,6-diamidino-2-phenylindol e (DAPI) confirming that FMR2 is a nuclear protein. The localization of FMR 2 protein to the mammalian hippocampus and other brain structures involved with cognitive function is consistent with the learning deficits seen in FR AXE individuals.