A HETEROGENEOUS SET OF FMR1 PROTEINS IS WIDELY DISTRIBUTED IN MOUSE-TISSUES AND IS MODULATED IN CELL-CULTURE

The fragile X syndrome is an X-linked inherited disease and is the res ult of transcriptional inactivation of the FMR1 gene and the absence o f its encoded FMR protein (FMRP), Using a specific monoclonal antibody directed against human FMRP, we have studied the steady-state levels of its murine homolog in several tissues and organs of adult and young mice, In immunoblot analyses, the antibody recognizes a heterogeneous subset of proteins with apparent molecular weights ranging from 80 to 70 kDa, These proteins are detected in all the 27 tissues tested; how ever, the relative proportion of each polypeptide recognized varies be tween tissues, and a significantly higher expression is observed in yo ung animals, Northern blot analysis of RNA extracted from selected tis sues from adult mouse shows that these tissues express the major 4.8 k b mRNA, although at different levels, and contain several additional s horter transcripts, particularly in muscular tissues, We also report t hat expression of the FMR1 gene is modulated in proliferating and quie scent primary mouse kidney eel! cultures with an inverse relationship between levels of FMR1 mRNA and of its encoded proteins. This suggests that FMRPs are highly stable in quiescent cells and that FMR1 express ion is likely posttranscriptionally controlled. Our results document t he widespread expression of the FMR1 gene, and suggest that it is cont rolled by different mechanisms implicated in cell growth and different iation.