A review and a research study: Fly models of Fragile X syndrome

Specchia V, Puricella A, D'Attis S, Massari S, Giangrande A, Bozzetti MP. Drosophila melanogaster as a Model to Study the Multiple Phenotypes, Related to Genome Stability of the Fragile-X Syndrome. Front Genet. 2019 Feb 13;10:10. PMID: 30815010; PMCID: PMC6381874.

Abstract: "Fragile-X syndrome is one of the most common forms of inherited mental retardation and autistic behaviors. The reduction/absence of the functional FMRP protein, coded by the X-linked Fmr1 gene in humans, is responsible for the syndrome. Patients exhibit a variety of symptoms predominantly linked to the function of FMRP protein in the nervous system like autistic behavior and mild-to-severe intellectual disability. Fragile-X (FraX) individuals also display cellular and morphological traits including branched dendritic spines, large ears, and macroorchidism. The dFmr1 gene is the Drosophila ortholog of the human Fmr1 gene. dFmr1 mutant flies exhibit synaptic abnormalities, behavioral defects as well as an altered germline development, resembling the phenotypes observed in FraX patients. Therefore, Drosophila melanogaster is considered a good model to study the physiopathological mechanisms underlying the Fragile-X syndrome. In this review, we explore how the multifaceted roles of the FMRP protein have been addressed in the Drosophila model and how the gained knowledge may open novel perspectives for understanding the molecular defects causing the disease and for identifying novel therapeutical targets."

Wang C, Ge L, Wu J, Wang X, Yuan L. MiR-219 represses expression of dFMR1 in Drosophila melanogaster. Life Sci. 2019 Feb 1;218:31-37. PMID: 30528775.

From the abstract: "... Here, we aimed to identify miRNAs regulating FMRP levels in Drosophila. ...
Using online software, we predicted and selected 11 miRNAs potentially acting on the Drosophila fragile X mental retardation 1 (dFMR1) transcript. ... Among the 11 miRNAs screened, miR-219 and miR-960 reduced luciferase gene activity by binding to the 3'-UTR of the dFMR1 transcript. Mutation of the miR-219 or miR-960 binding sites on the transcript resulted in complete or partial elimination of the miRNA-induced repression. Western blots revealed that dFMRP expression was decreased in the miR-219 overexpression model (Elav>miR-219). Drosophila larvae overexpressing miR-219 showed morphological abnormalities at the neuromuscular junction (increased synaptic boutons and synaptic branches). This finding is consistent with some phenotypes observed in dfmr1 mutants. ... Our results suggest that miR-219 regulates dFMR1 expression in Drosophila and is involved in fragile X syndrome pathogenesis. Collectively, these findings expand the current understanding of miRNA-mediated regulation of target molecule-related functions."