In all figures, numbers inside or above bars indicate number of mice per group unless indicated otherwise. ( A–E) Male Scn1a +/+ and Scn1a RX/+ mice with 2, 1, or 0 Mapt alleles were assessed for autism-like behaviors at 4–7 months of age. Our findings suggest an enabling role of tau in the pathogenesis of autism and identify tau reduction as a potential therapeutic strategy for some of the disorders that cause this condition.Īkt Cntnap2 PI3 kinase PTEN Scn1a Shank3 autism spectrum disorders mTOR megalencephaly tau.Ĭopyright © 2020 Elsevier Inc. We identify disinhibition of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a negative PI3K regulator that tau controls, as a plausible mechanism and demonstrate that tau interacts with PTEN via tau's proline-rich domain. All of these abnormalities were prevented or markedly diminished by partial or complete genetic removal of tau. Similar to a proportion of people with autism, both models have epilepsy, abnormally enlarged brains, and overactivation of the phosphatidylinositol 3-kinase (PI3K)/Akt (protein kinase B)/ mammalian target of rapamycin (mTOR) signaling pathway.

Here, we show that genetically reducing the protein tau prevents behavioral signs of autism in two mouse models simulating distinct causes of this condition. It is a prevalent neurodevelopmental disorder, and available treatments offer little benefit. Autism is characterized by repetitive behaviors, impaired social interactions, and communication deficits.

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