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.
abstract: The Fragile X syndrome (FXS) is the most frequent form of inherited mental disability and is considered a monogenic cause of autism spectrum disorder. FXS is caused by a triplet expansion that inhibits the expression of the FMR1 gene. The gene product, the Fragile X Mental Retardation Protein (FMRP), regulates mRNA metabolism in brain and nonneuronal cells. During brain development, FMRP controls the expression of key molecules involved in receptor signaling, cytoskeleton remodeling, protein synthesis and, ultimately, spine morphology. Symptoms associated with FXS include neurodevelopmental delay, cognitive impairment, anxiety, hyperactivity, and autistic-like behavior. Twenty years ago the first Fmr1 KO mouse to study FXS was generated, and several years later other key models including the mutant Drosophila melanogaster, dFmr1, have further helped the understanding of the cellular and molecular causes behind this complex syndrome. Here, we review to which extent these biological models are affected by the absence of FMRP, pointing out the similarities with the observed human dysfunction. Additionally, we discuss several potential treatments under study in animal models that are able to partially revert some of the FXS abnormalities.
authors.affiliation: VIB Center for the Biology of Disease, 3000 Leuven, Belgium Center for Human Genetics, KU Leuven, 3000 Leuven, Belgium Leuven Institute for Neurodegenerative Diseases (LIND), KU Leuven, 3000 Leuven, Belgium.
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Santos
authors.affiliation: VIB Center for the Biology of Disease, 3000 Leuven, Belgium Center for Human Genetics, KU Leuven, 3000 Leuven, Belgium Leuven Institute for Neurodegenerative Diseases (LIND), KU Leuven, 3000 Leuven, Belgium.
authors.forename: Alexandros K
authors.initials: AK
authors.lastname: Kanellopoulos
authors.affiliation: VIB Center for the Biology of Disease, 3000 Leuven, Belgium Center for Human Genetics, KU Leuven, 3000 Leuven, Belgium Leuven Institute for Neurodegenerative Diseases (LIND), KU Leuven, 3000 Leuven, Belgium Department of Biomedicine and Prevention, University of Rome "Tor Vergata" 00133, Rome, Italy claudia.bagni@uniroma2.it claudia.bagni@med.kuleuven.be.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bagni
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics; D002940:Circadian Rhythm / Q000235:genetics; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics* / Q000503:physiopathology*; D006801:Humans; D007858:Learning / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D055139:Sensory Gating / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D012919:Social Behavior
chemical_list: D029721:Drosophila Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; C467328:FMR1 protein, Drosophila; C497684:Fmr1 protein, mouse