title: Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) Motor Dysfunction Modeled in Mice.
abstract: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that affects some carriers of the fragile X premutation (PM). In PM carriers, there is a moderate expansion of a CGG trinucleotide sequence (55-200 repeats) in the fragile X gene (FMR1) leading to increased FMR1 mRNA and small to moderate decreases in the fragile X mental retardation protein (FMRP) expression. The key symptoms of FXTAS include cerebellar gait ataxia, kinetic tremor, sensorimotor deficits, neuropsychiatric changes, and dementia. While the specific trigger(s) that causes PM carriers to progress to FXTAS pathogenesis remains elusive, the use of animal models has shed light on the underlying neurobiology of the altered pathways involved in disease development. In this review, we examine the current use of mouse models to study PM and FXTAS, focusing on recent advances in the field. Specifically, we will discuss the construct, face, and predictive validities of these PM mouse models, the insights into the underlying disease mechanisms, and potential treatments.
authors.affiliation: Department of Neurological Surgery, University of California, Davis, CA, USA. mmfoote@ucdavis.edu.
authors.forename: Molly
authors.initials: M
authors.lastname: Foote
authors.affiliation: Department of Molecular Neuroscience, Medical University of Vienna, Vienna, Austria.
authors.forename: Gloria
authors.initials: G
authors.lastname: Arque
authors.affiliation: Department of Neurological Surgery, University of California, Davis, CA, USA.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Berman
authors.affiliation: Institute of Biology, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Mónica
authors.initials: M
authors.lastname: Santos
mesh_terms: D000818:Animals; D001259:Ataxia / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D004195:Disease Models, Animal; D005600:Fragile X Syndrome / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D014202:Tremor / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*
keywords: CGG trinucleotide repeat; Fragile X mental retardation (FMR1) gene; Fragile X premutation; Fragile X-associated tremor/ataxia syndrome (FXTAS); Mouse models; Neurodegenerative disorder