Autistic-Like Traits and Cerebellar Dysfunction in Purkinje Cell PTEN Knock-Out Mice.

Dario Cupolillo, Eriola Hoxha, Alessio Faralli, Annarita De Luca, Ferdinando Rossi, Filippo Tempia, Daniela Carulli
Neuropsychopharmacol. 2015-11-05; 41(6): 1457-1466
DOI: 10.1038/npp.2015.339

Read on PubMed

1. Neuropsychopharmacology. 2016 May;41(6):1457-66. doi: 10.1038/npp.2015.339. Epub
2015 Nov 5.

Autistic-Like Traits and Cerebellar Dysfunction in Purkinje Cell PTEN Knock-Out

Cupolillo D(1)(2), Hoxha E(1)(2), Faralli A(1)(2), De Luca A(1)(2), Rossi
F(1)(2), Tempia F(1)(2), Carulli D(1)(2).

Author information:
(1)Department of Neuroscience, Neuroscience Institute of Turin (NIT), University
of Turin, Turin, Italy.
(2)Neuroscience Institute of the Cavalieri-Ottolenghi Foundation (NICO),
University of Turin, Turin, Italy.

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.

DOI: 10.1038/npp.2015.339
PMCID: PMC4832032
PMID: 26538449 [Indexed for MEDLINE]

Know more about