Fragile X Related Gene Family: 3 Members Involved in Brain and Muscle Development pp. 283-301
Authors: (Elias Bechara, Mireille Melko, Barbara Bardoni, CNRS UMR 6543 – Université de Nice Sophia-Antipolis, Faculté de Médecine, Nice, France)
Abstract: Fragile X Mental Retardation protein (FMRP), together with its paralogous proteins Fragile X Related 1/2 (FXR1P) and (FXR2P) belongs to a family of RNA-binding proteins, named FXR (Fragile X Related) . Inactivation of FMR1 (the gene coding for FMRP) causes Fragile X syndrome, the most common cause of inherited mental retardation . The other members of this family, FXR1 and FXR2, are autosomal and have not been associated with any human disease so far. In vertebrates, members of the FXR protein family are structurally very similar and share a high degree of sequence homology in clustered regions corresponding to functional domains. The three proteins have similar functional domains: NLS, NES, two KH domains and an RNA-binding RGG box. Animal models have been generated in mouse, drosophila and zebrafish for Fmr1 deficiency, recapitulating the phenotype of Fragile X syndrome. In particular, in Fragile X patients as well as in all animal models the only brain abnormality that has been described is the presence of dendritic spines that are longer, thinner and denser than in normal individuals. Fxr2 null mice are viable and show some behavioural phenotypes, such as hyperactivity, similar to those observed in Fmr1 knockout mice. Interestingly, Fmr1/Fxr2 double knockout mice have exaggerated behavioural phenotypes when compared with single gene knockouts. These findings suggested that both FXR genes contribute in a cooperative manner to pathways controlling cognitive processes. Conversely, generation of Fxr1-null mice and frogs allowed to demonstrating that FXR1P is essential for normal muscle development.