Mouse models of fragile X-related disorders

Abstract

The fragile X-related disorders are an important group of hereditary disorders that are caused by expanded CGG repeats in the 5′ untranslated region of the FMR1 gene or by mutations in the coding sequence of this gene. Two categories of pathological CGG repeats are associated with these disorders, full mutation alleles and shorter premutation alleles. Individuals with full mutation alleles develop fragile X syndrome, which causes autism and intellectual disability, whereas those with premutation alleles, which have shorter CGG expansions, can develop fragile X-associated tremor/ataxia syndrome, a progressive neurodegenerative disease. Thus, fragile X-related disorders can manifest as neurodegenerative or neurodevelopmental disorders, depending on the size of the repeat expansion. Here, we review mouse models of fragile X-related disorders and discuss how they have informed our understanding of neurodegenerative and neurodevelopmental disorders. We also assess the translational value of these models for developing rational targeted therapies for intellectual disability and autism disorders.

From synapses to circuits: What mouse models have taught us about how autism spectrum disorder impacts hippocampal function

“…Both mouse (Bey and Jiang, 2014;Willemsen and Kooy, 2023) and rat (Engineer et al, 2014;Hamilton et al, 2014) models of FXS have been generated and subject to in vivo electrophysiological analysis. Two studies recorded from the CA1 region of Fmr1 -/mice performing an active place avoidance task Radwan et al, 2016) and observed changes in the temporal and spatial coordination of hippocampal oscillations in a cognitive state dependent manner, with alterations in the patterns of coupling between the theta and slow gamma rhythms, as well as an inflexibility of the spatial representations in the Fmr1 -/+ mice.…”