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Pten regulates neuronal arborization and social interaction in mice.

CNS deletion of Pten in the mouse has revealed its roles in controlling cell size and number, thus providing compelling etiology for macrocephaly and Lhermitte-Duclos disease. PTEN mutations in individuals with autism spectrum disorders (ASD) have also been reported, although a causal link between PTEN and ASD remains unclear. In the present study, we deleted Pten in limited differentiated neuronal populations in the cerebral cortex and hippocampus of mice. Resulting mutant mice showed abnormal social interaction and exaggerated responses to sensory stimuli. We observed macrocephaly and neuronal hypertrophy, including hypertrophic and ectopic dendrites and axonal tracts with increased synapses. This abnormal morphology was associated with activation of the Akt/mTor/S6k pathway and inactivation of Gsk3beta. Thus, our data suggest that abnormal activation of the PI3K/AKT pathway in specific neuronal populations can underlie macrocephaly and behavioral abnormalities reminiscent of certain features of human ASD.

Pubmed ID: 16675393

Authors

  • Kwon CH
  • Luikart BW
  • Powell CM
  • Zhou J
  • Matheny SA
  • Zhang W
  • Li Y
  • Baker SJ
  • Parada LF

Journal

Neuron

Publication Data

May 4, 2006

Associated Grants

  • Agency: Autism Speaks, Id: AS1270
  • Agency: NIMH NIH HHS, Id: K08 MH065975
  • Agency: NIMH NIH HHS, Id: K08 MH065975-03
  • Agency: NIMH NIH HHS, Id: K08 MH065975-04
  • Agency: NIMH NIH HHS, Id: K08 MH065975-05
  • Agency: NIMH NIH HHS, Id: MH06597503
  • Agency: NINDS NIH HHS, Id: NS44172
  • Agency: NIMH NIH HHS, Id: R01 MH081164
  • Agency: NINDS NIH HHS, Id: R37NS33199

Mesh Terms

  • Animals
  • Autistic Disorder
  • Axons
  • Behavior, Animal
  • Brain
  • Cell Differentiation
  • Cerebral Cortex
  • Dendrites
  • Disease Models, Animal
  • Glycogen Synthase Kinase 3
  • Hippocampus
  • Hypertrophy
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Mutation
  • Nervous System Malformations
  • Neurons
  • PTEN Phosphohydrolase
  • Proto-Oncogene Proteins c-akt
  • Reflex, Startle
  • Signal Transduction
  • Social Behavior