Learning and behavioral deficits associated with the absence of the fragile X mental retardation protein: what a fly and mouse model can teach us

AR Santos, AK Kanellopoulos, C Bagni - Learning & memory, 2014 - learnmem.cshlp.org
AR Santos, AK Kanellopoulos, C Bagni
Learning & memory, 2014learnmem.cshlp.org
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 …
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.
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