Cytoplasmic-predominant Pten increases microglial activation and synaptic pruning in a murine model with autism-like phenotype.

ABSTRACT: Germline mutations in PTEN account for ~10% of cases of autism spectrum disorder (ASD) with coincident macrocephaly. To explore the importance of nuclear PTEN in the development of ASD and macrocephaly, we previously generated a mouse model with predominantly cytoplasmic localization of Pten (Pten^m3m4/m3m4).Cytoplasmic predominant Pten localization results in a phenotype of extreme macrocephaly and autistic-like traits. Transcriptomic analysis of the Pten^m3m4/m3m4 cortex found upregulated gene pathways related to myeloid cell activation, myeloid cell migration, and phagocytosis. These transcriptomic findings were used to direct in vitro assays on Pten wild-type and Pten^m3m4/m3m4 microglia. We found increased Iba1 and C1q expression with enhanced phagocytic

SUBMITTER: Sarn N 

PROVIDER: S-EPMC8159731 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature