title: Autistic-Like Traits and Cerebellar Dysfunction in Purkinje Cell PTEN Knock-Out Mice.
abstract: Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impaired social interaction, isolated areas of interest, and insistence on sameness. Mutations in Phosphatase and tensin homolog missing on chromosome 10 (PTEN) have been reported in individuals with ASDs. Recent evidence highlights a crucial role of the cerebellum in the etiopathogenesis of ASDs. In the present study we analyzed the specific contribution of cerebellar Purkinje cell (PC) PTEN loss to these disorders. Using the Cre-loxP recombination system, we generated conditional knockout mice in which PTEN inactivation was induced specifically in PCs. We investigated PC morphology and physiology as well as sociability, repetitive behavior, motor learning, and cognitive inflexibility of adult PC PTEN-mutant mice. Loss of PTEN in PCs results in autistic-like traits, including impaired sociability, repetitive behavior and deficits in motor learning. Mutant PCs appear hypertrophic and show structural abnormalities in dendrites and axons, decreased excitability, disrupted parallel fiber and climbing fiber synapses and late-onset cell death. Our results unveil new roles of PTEN in PC function and provide the first evidence of a link between the loss of PTEN in PCs and the genesis of ASD-like traits.
authors.affiliation: Department of Neuroscience, Neuroscience Institute of Turin (NIT), University of Turin, Turin, Italy.|Neuroscience Institute of the Cavalieri-Ottolenghi Foundation (NICO), University of Turin, Turin, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Cupolillo
authors.affiliation: Department of Neuroscience, Neuroscience Institute of Turin (NIT), University of Turin, Turin, Italy.|Neuroscience Institute of the Cavalieri-Ottolenghi Foundation (NICO), University of Turin, Turin, Italy.
authors.forename: Eriola
authors.initials: E
authors.lastname: Hoxha
authors.affiliation: Department of Neuroscience, Neuroscience Institute of Turin (NIT), University of Turin, Turin, Italy.|Neuroscience Institute of the Cavalieri-Ottolenghi Foundation (NICO), University of Turin, Turin, Italy.
authors.forename: Alessio
authors.identifier: http://orcid.org/0000-0002-9487-1530
authors.initials: A
authors.lastname: Faralli
authors.affiliation: Department of Neuroscience, Neuroscience Institute of Turin (NIT), University of Turin, Turin, Italy.|Neuroscience Institute of the Cavalieri-Ottolenghi Foundation (NICO), University of Turin, Turin, Italy.
authors.forename: Annarita
authors.initials: A
authors.lastname: De Luca
authors.affiliation: Department of Neuroscience, Neuroscience Institute of Turin (NIT), University of Turin, Turin, Italy.|Neuroscience Institute of the Cavalieri-Ottolenghi Foundation (NICO), University of Turin, Turin, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Rossi
authors.affiliation: Department of Neuroscience, Neuroscience Institute of Turin (NIT), University of Turin, Turin, Italy.|Neuroscience Institute of the Cavalieri-Ottolenghi Foundation (NICO), University of Turin, Turin, Italy.
authors.forename: Filippo
authors.identifier: http://orcid.org/0000-0003-2778-0943
authors.initials: F
authors.lastname: Tempia
authors.affiliation: Department of Neuroscience, Neuroscience Institute of Turin (NIT), University of Turin, Turin, Italy.|Neuroscience Institute of the Cavalieri-Ottolenghi Foundation (NICO), University of Turin, Turin, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Carulli
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000503:physiopathology*; D002531:Cerebellum / Q000503:physiopathology*; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D051059:PTEN Phosphohydrolase / Q000502:physiology*; D011689:Purkinje Cells / Q000502:physiology*; D012919:Social Behavior; D065853:Spatial Learning / Q000502:physiology; D013239:Stereotyped Behavior / Q000502:physiology
chemical_list: D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse