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


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.

SUBMITTER: Igarashi A 

PROVIDER: S-EPMC6005449 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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

Igarashi Atsushi A   Itoh Kie K   Yamada Tatsuya T   Adachi Yoshihiro Y   Kato Takashi T   Murata Daisuke D   Sesaki Hiromi H   Iijima Miho M  

The Journal of biological chemistry 20180507 24


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 <i>in vivo</i> function of nuclear PTEN is unclear. Here, using CRISPR/Cas9, we generated a mouse model in which PTEN l  ...[more]

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