Nuclear PTEN Deficiency Causes Microcephaly with Decreased Neuronal Soma Size and Increased Seizure Susceptibility

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2018 May 9

PMID 29735527

Citations 20

Authors

Atsushi Igarashi

Kie Itoh

Tatsuya Yamada

Yoshihiro Adachi

Takashi Kato

Daisuke Murata

Hiromi Sesaki

Miho Iijima

Affiliations

Soon will be listed here.

Abstract

Defects in phosphatase and tensin homolog (PTEN) are associated with neurological disorders and tumors. PTEN functions at two primary intracellular locations: the plasma membrane and the nucleus. At the membrane, PTEN functions as a phosphatidylinositol (3,4,5)-trisphosphate phosphatase and suppresses PI 3-kinase signaling that drives cell growth and tumorigenesis. However, the function of nuclear PTEN is unclear. Here, using CRISPR/Cas9, we generated a mouse model in which PTEN levels in the nucleus are decreased. Nuclear PTEN-deficient mice were born with microcephaly and maintained a small brain during adulthood. The size of neuronal soma was significantly smaller in the cerebellum, cerebral cortex, and hippocampus. Also, these mice were prone to seizure. No changes in PI 3-kinase signaling were observed. By contrast, the size of other organs was unaffected. Therefore, nuclear PTEN is essential for the health of the brain by promoting the growth of neuronal soma size during development.

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