Nuclear PTEN deficiency causes microcephaly with decreased neuronal soma size and increased seizure susceptibility

Atsushi Igarashi, Kie Itoh, Tatsuya Yamada, Yoshihiro Adachi, Takashi Kato, Daisuke Murata, Hiromi Sesaki, Miho Iijima

Research output: Contribution to journalArticle

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 in vivo 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.

Original languageEnglish (US)
Pages (from-to)9292-9300
Number of pages9
JournalJournal of Biological Chemistry
Volume293
Issue number24
DOIs
StatePublished - Jun 15 2018

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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