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 expansion of a CGG repeat in the FMR-1 gene. In patients with a full mutation, abnormal methylation results in suppression of FMR-1 transcription. FMR-1 is expressed in many tissues but its function is unknown. We have raised monoclonal antibodies specific for the FMR-1 protein. They detect 4-5 protein bands which appear identical in cells of normal males and of males carrying a premutation, but are absent in affected males with a full mutation. Immunohistochemistry shows a cytoplasmic localization of FMR-1. The highest levels were observed in neurons, while glial cells contain very low levels. In epithelial tissues, levels of FMR-1 were higher in dividing layers. In adult testis, FMR-1 was detected only in spermatogonia. FMR-1 was not detected in dermis and cardiac muscle except under pathological conditions.