Abnormal neurodevelopment, neurosignaling and behaviour in Npas3-deficient mice

Eric W. Brunskill, Lisa A. Ehrman, Michael T. Williams, Justin Klanke, Daniel Hammer, Tori L. Schaefer, Renu Sah, Gerald W. Dorn, S. Steven Potter, Charles V. Vorhees

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Npas3 is a member of the bHLH-PAS superfamily of transcription factors that is expressed broadly in the developing neuroepithelium. To study the function of this gene, mice deficient in Npas3 were generated and characterized. Npas3-/- mice were growth-retarded and exhibited developmental brain abnormalities that included a reduction in size of the anterior hippocampus, hypoplasia of the corpus callosum and enlargement of the ventricles. A number of behavioural abnormalities were identified in Npas3-/- mice including locomotor hyperactivity, subtle gait defects, impairment of prepulse inhibition of acoustic startle, deficit in recognition memory and altered anxiety-related responses. Characterization of neurosignaling pathways using several pharmacological agents revealed dysfunctional glutamate, dopamine and serotonin neurotransmitter signaling. Consistent with these findings, we identified a significant alteration in cortical PSD-95 expression, a PDZ-containing protein that has been shown to be involved in postsynaptic signal transduction. Together, our observations indicate an important role for Npas3 in controlling normal brain development and neurosignaling pathways.

Original languageEnglish
Pages (from-to)1265-1276
Number of pages12
JournalEuropean Journal of Neuroscience
Volume22
Issue number6
DOIs
StatePublished - Sep 2005

Keywords

  • Behavioural abnormalities
  • Brain development
  • Developing neuroepithelium
  • Developmental abnormalities
  • PSD-95
  • bHLH-PAS

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