{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T11:32:16Z","timestamp":1762083136608,"version":"build-2065373602"},"reference-count":105,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T00:00:00Z","timestamp":1672185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science Fund of the Republic of Serbia, Program IDEA","award":["7673781","451-03-68\/2022-14\/200178"],"award-info":[{"award-number":["7673781","451-03-68\/2022-14\/200178"]}]},{"name":"Serbian Ministry of Education, Science and Technological Development","award":["7673781","451-03-68\/2022-14\/200178"],"award-info":[{"award-number":["7673781","451-03-68\/2022-14\/200178"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Fragile X syndrome (FXS) is a global neurodevelopmental disorder caused by the expansion of CGG trinucleotide repeats (\u2265200) in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene. FXS is the hallmark of Fragile X-associated disorders (FXD) and the most common monogenic cause of inherited intellectual disability and autism spectrum disorder. There are several animal models used to study FXS. In the FXS model of Drosophila, the only ortholog of FMR1, dfmr1, is mutated so that its protein is missing. This model has several relevant phenotypes, including defects in the circadian output pathway, sleep problems, memory deficits in the conditioned courtship and olfactory conditioning paradigms, deficits in social interaction, and deficits in neuronal development. In addition to FXS, a model of another FXD, Fragile X-associated tremor\/ataxia syndrome (FXTAS), has also been established in Drosophila. This review summarizes many years of research on FXD in Drosophila models.<\/jats:p>","DOI":"10.3390\/genes14010087","type":"journal-article","created":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T08:42:22Z","timestamp":1672216942000},"page":"87","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Drosophila melanogaster as a Model to Study Fragile X-Associated Disorders"],"prefix":"10.3390","volume":"14","author":[{"given":"Jelena","family":"Trajkovi\u0107","sequence":"first","affiliation":[{"name":"Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vedrana","family":"Makevic","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milica","family":"Pesic","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofija","family":"Pavkovi\u0107-Lu\u010di\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Milojevic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Smiljana","family":"Cvjetkovic","sequence":"additional","affiliation":[{"name":"Department of Humanities, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5029-8448","authenticated-orcid":false,"given":"Randi","family":"Hagerman","sequence":"additional","affiliation":[{"name":"Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis, 2825 50th Street, Sacramento, CA 95817, USA"},{"name":"Department of Pediatrics, University of California Davis School of Medicine, Sacramento, CA 95817, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7263-5134","authenticated-orcid":false,"given":"Dejan B.","family":"Budimirovic","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Fragile X Clinic, Kennedy Krieger Institute, Baltimore, MD 21205, USA"},{"name":"Department of Psychiatry & Behavioral Sciences-Child Psychiatry, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2137-5405","authenticated-orcid":false,"given":"Dragana","family":"Protic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,28]]},"reference":[{"key":"ref_1","unstructured":"King, R.C. (1965). Genetics, Oxford University Press. [2nd ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Fuentes, E., Sivakumar, N., Selvik, L.-K., Arch, M., Cardona, P.J., Ioerger, T.R., and Dragset, M.S. (2022). Drosophila melanogaster is a powerful host model to study mycobacterial virulence. bioRxiv.","DOI":"10.1101\/2022.05.12.491628"},{"key":"ref_3","unstructured":"Russell, W.M.S., and Burch, R.L. (1959). The Principles of Humane Experimental Technique, Methuen & Co, Ltd."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1126\/science.287.5461.2185","article-title":"The genome sequence of Drosophila melanogaster","volume":"287","author":"Adams","year":"2000","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2196","DOI":"10.1126\/science.287.5461.2196","article-title":"A whole-genome assembly of Drosophila","volume":"287","author":"Myers","year":"2000","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"research0079.1","DOI":"10.1186\/gb-2002-3-12-research0079","article-title":"Finishing a whole-genome shotgun: Release 3 of the Drosophila melanogaster euchromatic genome sequence","volume":"3","author":"Celniker","year":"2002","journal-title":"Genome Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/nature12962","article-title":"Diversity and dynamics of the Drosophila transcriptome","volume":"512","author":"Brown","year":"2014","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1534\/genetics.117.199950","article-title":"A Short History and Description of Drosophila melanogaster Classical Genetics: Chromosome Aberrations, Forward Genetic Screens, and the Nature of Mutations","volume":"206","author":"Kaufman","year":"2017","journal-title":"Genetics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.cell.2014.09.002","article-title":"A Drosophila Genetic Resource of Mutants to Study Mechanisms Underlying Human Genetic Diseases","volume":"159","author":"Yamamoto","year":"2014","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1242\/dmm.023762","article-title":"Drosophila tools and assays for the study of human diseases","volume":"9","author":"Ugur","year":"2016","journal-title":"Dis. Model. Mech."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0070-2153(09)88002-2","article-title":"Chapter 2 Evolution of the Hox Gene Complex from an Evolutionary Ground State","volume":"Volume 88","author":"Gehring","year":"2009","journal-title":"Current Topics in Developmental Biology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/S1369-7021(11)70113-4","article-title":"Drosophila\u2013a versatile model in biology & medicine","volume":"14","author":"Jennings","year":"2011","journal-title":"Mater. Today"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/7854_2010_110","article-title":"Drosophila as a model organism for the study of neuropsychiatric disorders","volume":"7","year":"2011","journal-title":"Curr. Top Behav. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1080\/19336934.2022.2087484","article-title":"Studies of neurodegenerative diseases using Drosophila and the development of novel approaches for their analysis","volume":"16","author":"Nitta","year":"2022","journal-title":"Fly"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"R11","DOI":"10.1016\/j.cub.2009.10.031","article-title":"The mushroom body","volume":"20","author":"Campbell","year":"2010","journal-title":"Curr. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-981-13-0529-0_1","article-title":"Drosophila as a Model Organism","volume":"Volume 1076","author":"Yamaguchi","year":"2018","journal-title":"Drosophila Models for Human Diseases"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/nrn2839","article-title":"100 years of Drosophila research and its impact on vertebrate neuroscience: A history lesson for the future","volume":"11","author":"Bellen","year":"2010","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0168-9525(99)01939-3","article-title":"Modeling human neurodegenerative diseases in Drosophila: On a wing and a prayer","volume":"16","author":"Fortini","year":"2000","journal-title":"Trends Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/nrn751","article-title":"Modelling neurodegenerative diseases in Drosophila: A fruitful approach?","volume":"3","author":"Muqit","year":"2002","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"dmm049549","DOI":"10.1242\/dmm.049549","article-title":"The power of Drosophila in modeling human disease mechanisms","volume":"15","author":"Verheyen","year":"2022","journal-title":"Dis. Model. Mech."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"124","DOI":"10.3389\/fnmol.2018.00124","article-title":"Modeling Fragile X Syndrome in Drosophila","volume":"11","author":"Drozd","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Curnow, E., and Wang, Y. (2022). New Animal Models for Understanding FMRP Functions and FXS Pathology. Cells, 11.","DOI":"10.3390\/cells11101628"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/0092-8674(91)90397-H","article-title":"Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome","volume":"65","author":"Verkerk","year":"1991","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5395","DOI":"10.1073\/pnas.94.10.5395","article-title":"Fragile X mental retardation protein is translated near synapses in response to neurotransmitter activation","volume":"94","author":"Weiler","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1523\/JNEUROSCI.17-05-01539.1997","article-title":"Fragile X mental retardation protein: Nucleocytoplasmic shuttling and association with somatodendritic ribosomes","volume":"17","author":"Feng","year":"1997","journal-title":"J. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1001\/jama.2008.684","article-title":"Testing for fragile X gene mutations throughout the life span","volume":"300","author":"Hagerman","year":"2008","journal-title":"JAMA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1093\/hmg\/1.6.397","article-title":"DNA methylation represses FMR-1 transcription in fragile X syndrome","volume":"1","author":"Sutcliffe","year":"1992","journal-title":"Hum. Mol. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"190","DOI":"10.25100\/cm.v45i4.1810","article-title":"Fragile X Syndrome","volume":"45","author":"Saldarriaga","year":"2014","journal-title":"Colomb. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/gm401","article-title":"FMR1 CGG allele size and prevalence ascertained through newborn screening in the United States","volume":"4","author":"Tassone","year":"2012","journal-title":"Genome Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/ng0893-335","article-title":"The FMR-1 protein is cytoplasmic, most abundant in neurons and appears normal in carriers of a fragile X premutation","volume":"4","author":"Devys","year":"1993","journal-title":"Nat. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/1096-8628(200022)97:2<153::AID-AJMG7>3.0.CO;2-M","article-title":"FMR1 gene and fragile X syndrome","volume":"97","author":"Bardoni","year":"2000","journal-title":"Am. J. Med. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1002\/jemt.10064","article-title":"Fragile X syndrome, the Fragile X related proteins, and animal models","volume":"57","author":"Hoogeveen","year":"2002","journal-title":"Microsc. Res. Tech."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S1462399406010751","article-title":"The fragile X syndrome: Exploring its molecular basis and seeking a treatment","volume":"8","author":"Bardoni","year":"2006","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.neubiorev.2014.01.006","article-title":"Fragile X Syndrome: From molecular pathology to therapy","volume":"46","author":"Maurin","year":"2014","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1093\/hmg\/ddm263","article-title":"The fragile X mental retardation protein is a molecular adaptor between the neurospecific KIF3C kinesin and dendritic RNA granules","volume":"16","author":"Davidovic","year":"2007","journal-title":"Hum Mol. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"104796","DOI":"10.1155\/2012\/104796","article-title":"Mechanism of repeat-associated microRNAs in fragile X syndrome","volume":"2012","author":"Kelley","year":"2012","journal-title":"Neural Plast."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Specchia, V., D\u2019Attis, S., Puricella, A., and Bozzetti, M.P. (2017). dFmr1 Plays Roles in Small RNA Pathways of Drosophila melanogaster. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18051066"},{"key":"ref_38","unstructured":"Johnston, M., Michael, A.M., Fatemi, M.H., and Ali, M.B.A. (2016). Neurobiology of Autism and Intellectual Disability: Fragile X Syndrome. Neurobiology of Disease, Oxford University Press. [2nd ed.]."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"17065","DOI":"10.1038\/nrdp.2017.65","article-title":"Fragile X syndrome","volume":"3","author":"Hagerman","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1002\/ajmg.a.32439","article-title":"Co-occurring conditions associated with FMR1 gene variations: Findings from a national parent survey","volume":"146A","author":"Bailey","year":"2008","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"S194","DOI":"10.1542\/peds.2016-1159F","article-title":"Autism Spectrum Disorder in Fragile X Syndrome: Cooccurring Conditions and Current Treatment","volume":"139","author":"Kaufmann","year":"2017","journal-title":"Pediatrics"},{"key":"ref_42","unstructured":"Budimirovic, D., Haas-Givler, B., Blitz, R., Esler, A., Kaufmann, W., Sudhalter, V., Stackhouse, T.M., Scharfenaker, S.K., and Berry-Kravis, E. (2022, October 05). Autism Spectrum Disorder in Fragile X Syndrome. Available online: https:\/\/fragilex.org\/wp-content\/uploads\/2012\/08\/Autism-Spectrum-Disorder-in-Fragile-X-Syndrome-2014-Nov.pdf."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1002\/ajmg.a.62601","article-title":"Sleep problems in fragile X syndrome: Cross-sectional analysis of a large clinic-based cohort","volume":"188","author":"Budimirovic","year":"2022","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"736255","DOI":"10.3389\/fped.2021.736255","article-title":"Seizures in Fragile X Syndrome: Associations and Longitudinal Analysis of a Large Clinic-Based Cohort","volume":"9","author":"Filipink","year":"2021","journal-title":"Front. Pediatr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1002\/oby.23368","article-title":"Height and BMI in fragile X syndrome: A longitudinal assessment","volume":"30","author":"Choo","year":"2022","journal-title":"Obesity"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Hagerman, R.J., and Hagerman, P.J. (2020). Fragile X Syndrome and Premutation Disorders, Mac Keith Press.","DOI":"10.1002\/9781119432692.ch28"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"41","DOI":"10.3389\/fnmol.2018.00041","article-title":"Of Men and Mice: Modeling the Fragile X Syndrome","volume":"11","author":"Dahlhaus","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"8536","DOI":"10.1128\/MCB.20.22.8536-8547.2000","article-title":"Characterization of dFMR1, a Drosophila melanogaster homolog of the fragile X mental retardation protein","volume":"20","author":"Wan","year":"2000","journal-title":"Mol. Cell Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/S0092-8674(01)00589-X","article-title":"Drosophila fragile X-related gene regulates the MAP1B homolog Futsch to control synaptic structure and function","volume":"107","author":"Zhang","year":"2001","journal-title":"Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/S0896-6273(02)00731-6","article-title":"Drosophila Fragile X Protein, DFXR, Regulates Neuronal Morphology and Function in the Brain","volume":"34","author":"Morales","year":"2002","journal-title":"Neuron"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"E99","DOI":"10.1073\/pnas.1309543111","article-title":"FMRP and Ataxin-2 function together in long-term olfactory habituation and neuronal translational control","volume":"111","author":"Sudhakaran","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1016\/j.cub.2004.09.085","article-title":"The Drosophila fragile X gene negatively regulates neuronal elaboration and synaptic differentiation","volume":"14","author":"Pan","year":"2004","journal-title":"Curr. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1016\/S0960-9822(02)01036-9","article-title":"A role for the Drosophila fragile X-related gene in circadian output","volume":"12","author":"Inoue","year":"2002","journal-title":"Curr. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S0896-6273(02)00724-9","article-title":"Drosophila lacking dfmr1 activity show defects in circadian output and fail to maintain courtship interest","volume":"34","author":"Dockendorff","year":"2002","journal-title":"Neuron"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e129","DOI":"10.1016\/j.ddtec.2012.09.005","article-title":"Using Drosophila as a tool to identify Pharmacological Therapies for Fragile X Syndrome","volume":"10","author":"McBride","year":"2012","journal-title":"Drug Discov. Today Technol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/S0896-6273(03)00354-4","article-title":"CYFIP\/Sra-1 controls neuronal connectivity in Drosophila and links the Rac1 GTPase pathway to the fragile X protein","volume":"38","author":"Schenck","year":"2003","journal-title":"Neuron"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"10","DOI":"10.3389\/fgene.2019.00010","article-title":"Drosophila melanogaster as a Model to Study the Multiple Phenotypes, Related to Genome Stability of the Fragile-X Syndrome","volume":"10","author":"Specchia","year":"2019","journal-title":"Front. Genet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/j.cub.2004.05.055","article-title":"The fragile X-related gene affects the crawling behavior of Drosophila larvae by regulating the mRNA level of the DEG\/ENaC protein pickpocket1","volume":"14","author":"Xu","year":"2004","journal-title":"Curr. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"27972","DOI":"10.1038\/srep27972","article-title":"Quantifying and predicting Drosophila larvae crawling phenotypes","volume":"6","author":"Nettesheim","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1126\/science.8128246","article-title":"Loss of circadian behavioral rhythms and per RNA oscillations in the Drosophila mutant timeless","volume":"263","author":"Sehgal","year":"1994","journal-title":"Science"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1038\/nn.2175","article-title":"Excess protein synthesis in Drosophila Fragile X mutants impairs long-term memory","volume":"11","author":"Bolduc","year":"2008","journal-title":"Nat. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"216","DOI":"10.4161\/fly.4.3.12280","article-title":"An assay for social interaction in Drosophila fragile X mutants","volume":"4","author":"Bolduc","year":"2010","journal-title":"Fly"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1146\/annurev-med-081117-041238","article-title":"Metformin for Treatment of Fragile X Syndrome and Other Neurological Disorders","volume":"70","author":"Gantois","year":"2019","journal-title":"Annu. Rev. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"145","DOI":"10.5664\/jcsm.27443","article-title":"The efficacy of melatonin for sleep problems in children with autism, fragile X syndrome, or autism and fragile X syndrome","volume":"5","author":"Wirojanan","year":"2009","journal-title":"J. Clin. Sleep Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1093\/hmg\/ddu737","article-title":"The Fragile X proteins Fmrp and Fxr2p cooperate to regulate glucose metabolism in mice","volume":"24","author":"Lumaban","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Xu, S., Poidevin, M., Han, E., Bi, J., and Jin, P. (2012). Circadian rhythm-dependent alterations of gene expression in Drosophila brain lacking fragile X mental retardation protein. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0037937"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1523\/JNEUROSCI.4830-08.2009","article-title":"The Drosophila Fragile X Mental Retardation Gene Regulates Sleep Need","volume":"29","author":"Bushey","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"561","DOI":"10.2108\/zsj.25.561","article-title":"Circadian phenotypes of Drosophila fragile x mutants in alternative genetic backgrounds","volume":"25","author":"Sekine","year":"2008","journal-title":"Zoolog. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/978-3-642-21649-7_6","article-title":"Behavior in a Drosophila Model of Fragile X","volume":"Volume 54","author":"Denman","year":"2012","journal-title":"Modeling Fragile X Syndrome"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/01677063.2020.1833005","article-title":"Spontaneous motor-behavior abnormalities in two Drosophila models of neurodevelopmental disorders","volume":"35","author":"Andrew","year":"2021","journal-title":"J. Neurogenet."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"6917","DOI":"10.1523\/JNEUROSCI.0061-13.2013","article-title":"A dynamic deep sleep stage in Drosophila","volume":"33","author":"Yap","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"104740","DOI":"10.1016\/j.nbd.2020.104740","article-title":"Fragile X syndrome and associated disorders: Clinical aspects and pathology","volume":"136","author":"Dufour","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"eaai8133","DOI":"10.1126\/scisignal.aai8133","article-title":"Hyperactive locomotion in a Drosophila model is a functional readout for the synaptic abnormalities underlying fragile X syndrome","volume":"10","author":"Kashima","year":"2017","journal-title":"Sci. Signal"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1101\/lm.035956.114","article-title":"Learning and behavioral deficits associated with the absence of the fragile X mental retardation protein: What a fly and mouse model can teach us","volume":"21","author":"Santos","year":"2014","journal-title":"Learn. Mem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/dneu.20388","article-title":"Age-related changes in climbing behavior and neural circuit physiology in Drosophila","volume":"67","author":"Martinez","year":"2007","journal-title":"Dev. Neurobiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1136\/jmg.2008.059055","article-title":"The fragile X prevalence paradox","volume":"45","author":"Hagerman","year":"2008","journal-title":"J. Med. Genet."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1016\/S0140-6736(03)14471-6","article-title":"Autism","volume":"362","author":"Volkmar","year":"2003","journal-title":"Lancet"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Tauber, J.M., Vanlandingham, P.A., and Zhang, B. (2011). Elevated Levels of the Vesicular Monoamine Transporter and a Novel Repetitive Behavior in the Drosophila Model of Fragile X Syndrome. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0027100"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4101","DOI":"10.1007\/s10803-015-2536-0","article-title":"Violations of Personal Space in Young People with Autism Spectrum Disorders and Williams Syndrome: Insights from the Social Responsiveness Scale","volume":"45","author":"Lough","year":"2015","journal-title":"J. Autism. Dev. Disord."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s10522-009-9259-6","article-title":"Age-dependent cognitive impairment in a Drosophila fragile X model and its pharmacological rescue","volume":"11","author":"Choi","year":"2010","journal-title":"Biogerontology"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"6782","DOI":"10.1523\/JNEUROSCI.6369-09.2010","article-title":"Short- and long-term memory are modulated by multiple isoforms of the fragile X mental retardation protein","volume":"30","author":"Banerjee","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.neuron.2005.01.038","article-title":"Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of fragile X syndrome","volume":"45","author":"McBride","year":"2005","journal-title":"Neuron"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/nchembio.78","article-title":"Identification of small molecules rescuing fragile X syndrome phenotypes in Drosophila","volume":"4","author":"Chang","year":"2008","journal-title":"Nat. Chem. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1126\/science.8209251","article-title":"The mating of a fly","volume":"264","author":"Hall","year":"1994","journal-title":"Science"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Kim, K., Hessl, D., Randol, J.L., Espinal, G.M., Schneider, A., Protic, D., Aydin, E.Y., Hagerman, R.J., and Hagerman, P.J. (2019). Association between IQ and FMR1 protein (FMRP) across the spectrum of CGG repeat expansions. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0226811"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Budimirovic, D.B., Schlageter, A., Filipovic-Sadic, S., Protic, D.D., Bram, E., Mahone, E.M., Nicholson, K., Culp, K., Javanmardi, K., and Kemppainen, J. (2020). A Genotype-Phenotype Study of High-Resolution FMR1 Nucleic Acid and Protein Analyses in Fragile X Patients with Neurobehavioral Assessments. Brain Sci., 10.","DOI":"10.21203\/rs.3.rs-34874\/v1"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1093\/hmg\/ddr527","article-title":"In vivo neuronal function of the fragile X mental retardation protein is regulated by phosphorylation","volume":"21","author":"Coffee","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1055\/s-0031-1280915","article-title":"FMR1 and the continuum of primary ovarian insufficiency","volume":"29","author":"Sullivan","year":"2011","journal-title":"Semin. Reprod. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00401-013-1138-1","article-title":"Fragile X-associated tremor\/ataxia syndrome (FXTAS): Pathology and mechanisms","volume":"126","author":"Hagerman","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1212\/WNL.57.1.127","article-title":"Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X","volume":"57","author":"Hagerman","year":"2001","journal-title":"Neurology"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"564","DOI":"10.3389\/fpsyt.2018.00564","article-title":"Fragile X-Associated Neuropsychiatric Disorders (FXAND)","volume":"9","author":"Hagerman","year":"2018","journal-title":"Front. Psychiatry"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Cabal-Herrera, A.M., Tassanakijpanich, N., Salcedo-Arellano, M.J., and Hagerman, R.J. (2020). Fragile X-Associated Tremor\/Ataxia Syndrome (FXTAS): Pathophysiology and Clinical Implications. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124391"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1001\/jama.291.4.460","article-title":"Penetrance of the fragile X-associated tremor\/ataxia syndrome in a premutation carrier population","volume":"291","author":"Jacquemont","year":"2004","journal-title":"JAMA"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"3871","DOI":"10.1042\/BCJ20160585","article-title":"Plasma metabolic profile delineates roles for neurodegeneration, pro-inflammatory damage and mitochondrial dysfunction in the FMR1 premutation","volume":"473","author":"Giulivi","year":"2016","journal-title":"Biochem. J."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/S0896-6273(03)00533-6","article-title":"RNA-mediated neurodegeneration caused by the fragile X premutation rCGG repeats in Drosophila","volume":"39","author":"Jin","year":"2003","journal-title":"Neuron"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1093\/hmg\/dds024","article-title":"Chemical screen reveals small molecules suppressing fragile X premutation rCGG repeat-mediated neurodegeneration in Drosophila","volume":"21","author":"Qurashi","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.neuron.2013.03.026","article-title":"CGG repeat-associated translation mediates neurodegeneration in fragile X tremor ataxia syndrome","volume":"78","author":"Todd","year":"2013","journal-title":"Neuron"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.neuron.2007.07.020","article-title":"Pur alpha binds to rCGG repeats and modulates repeat-mediated neurodegeneration in a Drosophila model of fragile X tremor\/ataxia syndrome","volume":"55","author":"Jin","year":"2007","journal-title":"Neuron"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.neuron.2007.07.021","article-title":"RNA-binding proteins hnRNP A2\/B1 and CUGBP1 suppress fragile X CGG premutation repeat-induced neurodegeneration in a Drosophila model of FXTAS","volume":"55","author":"Sofola","year":"2007","journal-title":"Neuron"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1097\/DBP.0b013e318287cd17","article-title":"A randomized double-blind, placebo-controlled trial of minocycline in children and adolescents with fragile x syndrome","volume":"34","author":"Leigh","year":"2013","journal-title":"J. Dev. Behav. Pediatr."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1038\/mp.2016.51","article-title":"Insulin signaling misregulation underlies circadian and cognitive deficits in a Drosophila fragile X model","volume":"22","author":"Monyak","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e956","DOI":"10.1002\/mgg3.956","article-title":"Metformin treatment in young children with fragile X syndrome","volume":"7","author":"Biag","year":"2019","journal-title":"Mol. Genet. Genomic Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1111\/cge.13039","article-title":"Metformin as targeted treatment in fragile X syndrome","volume":"93","author":"Dy","year":"2018","journal-title":"Clin. Genet."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e00745","DOI":"10.1002\/mgg3.745","article-title":"Cognitive and behavioral improvement in adults with fragile X syndrome treated with metformin-two cases","volume":"7","author":"Protic","year":"2019","journal-title":"Mol. Genet. Genomic Med."},{"key":"ref_105","first-page":"100021","article-title":"Prepubertal Metformin Treatment in Fragile X Syndrome Alleviated Macroorchidism: A Case Study","volume":"3","author":"Protic","year":"2019","journal-title":"Adv. Clin. Transl. Res."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/1\/87\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:53:37Z","timestamp":1760147617000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/1\/87"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,28]]},"references-count":105,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["genes14010087"],"URL":"https:\/\/doi.org\/10.3390\/genes14010087","relation":{},"ISSN":["2073-4425"],"issn-type":[{"type":"electronic","value":"2073-4425"}],"subject":[],"published":{"date-parts":[[2022,12,28]]}}}