The parvalbumin/somatostatin ratio is increased in Pten mutant mice and by human PTEN ASD alleles

Cell Rep. 2015 May 12;11(6):944-956. doi: 10.1016/j.celrep.2015.04.019. Epub 2015 Apr 30.


Mutations in the phosphatase PTEN are strongly implicated in autism spectrum disorder (ASD). Here, we investigate the function of Pten in cortical GABAergic neurons using conditional mutagenesis in mice. Loss of Pten results in a preferential loss of SST(+) interneurons, which increases the ratio of parvalbumin/somatostatin (PV/SST) interneurons, ectopic PV(+) projections in layer I, and inhibition onto glutamatergic cortical neurons. Pten mutant mice exhibit deficits in social behavior and changes in electroencephalogram (EEG) power. Using medial ganglionic eminence (MGE) transplantation, we test for cell-autonomous functional differences between human PTEN wild-type (WT) and ASD alleles. The PTEN ASD alleles are hypomorphic in regulating cell size and the PV/SST ratio in comparison to WT PTEN. This MGE transplantation/complementation assay is efficient and is generally applicable for functional testing of ASD alleles in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Animals
  • Autism Spectrum Disorder / genetics*
  • Cell Count
  • Cell Death
  • Cell Proliferation
  • Cell Shape
  • Electroencephalography
  • GABAergic Neurons / metabolism
  • Gamma Rhythm
  • Humans
  • Integrases / metabolism
  • Interneurons / metabolism
  • Interpersonal Relations
  • Median Eminence / metabolism
  • Mice
  • Mutation / genetics*
  • Neural Stem Cells / metabolism
  • PTEN Phosphohydrolase / genetics*
  • Parvalbumins / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pyramidal Cells / metabolism
  • Signal Transduction
  • Somatostatin / metabolism*


  • Parvalbumins
  • Somatostatin
  • Proto-Oncogene Proteins c-akt
  • Cre recombinase
  • Integrases
  • PTEN Phosphohydrolase