THE FMR-1 PROTEIN IS CYTOPLASMIC, MOST ABUNDANT IN NEURONS AND APPEARS NORMAL IN CARRIERS OF A FRAGILE X PREMUTATION

Fragile X mental retardation syndrome is caused by the unstable expans ion of a CGG repeat in the FMR-1 gene. In patients with a full mutatio n, abnormal methylation results in suppression of FMR-1 transcription. FMR-1 is expressed in many tissues but its function is unknown. We ha ve raised monoclonal antibodies specific for the FMR-1 protein. They d etect 4-5 protein bands which appear identical in cells of normal male s and of males carrying a premutation, but are absent in affected male s with a full mutation. Immunohistochemistry shows a cytoplasmic local ization of FMR-1. The highest levels were observed in neurons, while g lial cells contain very low levels. In epithelial tissues, levels of F MR-1 were higher in dividing layers. In adult testis, FMR-1 was detect ed only in spermatogonia. FMR-1 was not detected in dermis and cardiac muscle except under pathological conditions.