Genetic Suppression of mTOR Rescues Synaptic and Social Behavioral Abnormalities in a Mouse Model of Pten Haploinsufficiency.

ABSTRACT: Heterozygous mutations in PTEN, which encodes a negative regulator of the mTOR and β-catenin signaling pathways, cause macrocephaly/autism syndrome. However, the neurobiological substrates of the core symptoms of this syndrome are poorly understood. Here, we investigate the relationship between cerebral cortical overgrowth and social behavior deficits in conditional Pten heterozygous female mice (Pten cHet) using Emx1-Cre, which is expressed in cortical pyramidal neurons and a subset of glia. We found that conditional heterozygous mutation of Ctnnb1 (encoding β-catenin) suppresses Pten cHet cortical overgrowth, but not social behavioral deficits, whereas conditional heterozygous mutation of Mtor suppresses social behavioral deficits, but not cortical overgrowth. Neuronal activity in respon

SUBMITTER: Huang WC 

PROVIDER: S-EPMC7141489 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature