Autistic-Like Traits and Cerebellar Dysfunction in Purkinje Cell PTEN Knock-Out Mice View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-05

AUTHORS

Dario Cupolillo, Eriola Hoxha, Alessio Faralli, Annarita De Luca, Ferdinando Rossi, Filippo Tempia, Daniela Carulli

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. More... »

PAGES

1457-1466

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/npp.2015.339

DOI

http://dx.doi.org/10.1038/npp.2015.339

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1003095929

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26538449


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