Cited by 84Neurogenesis and neuroplasticity mechanismsGenetics and Neurodevelopmental DisordersNeuroscience and Neuropharmacology Research

Abnormal neurodevelopment, neurosignaling and behaviour in Npas3-deficient mice

Brunskill, Eric W., Ehrman, Lisa A., Williams, Michael T., Klanke, Justin, Hammer, Daniel, Schaefer, Tori L., Sah, Renu, Il, Gerald W. Dorn +2 more·2005·European Journal of Neuroscience

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.

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Crossref · 10.1111/j.1460-9568.2005.04291.x

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Authors
Brunskill, E. W., Ehrman, L. A., Williams, M. T., Klanke, J., Hammer, D., Schaefer, T. L., Sah, R., Il, G. W. D., Potter, S. S., & Vorhees, C. V.
Affiliations
  • University of Cincinnati (US)
  • Cincinnati Children's Hospital Medical Center (US)
Corresponding author
Brunskill, Eric W.
Venue
European Journal of Neuroscience
Publisher
Wiley
Published
2005-09
Volume
22
Issue
6
Pages
1265-1276
ISSN
  • 0953-816X (ISSN-L)
  • 1460-9568
OpenAlex
W1566594410
Cited by
84
References
54
Citations by year
2026: 4 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 5 · 2016: 6 · 2015: 6 · 2014: 2 · 2013: 4 · 2012: 4
FWCI
1.23
Type
journal article
Language
en
Open access
closed
Locations
  • European Journal of Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Heart, Lung, and Blood Institute (HL58010, R01HL058010)
  • National Institute on Drug Abuse (DA14269, K01DA014269, R01DA006733, DA06733)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK061916, DK61916)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
NPAS3, bHLH-PAS transcription factors, brain development, corpus callosum hypoplasia, ventriculomegaly, locomotor hyperactivity, prepulse inhibition, recognition memory, anxiety, glutamate signaling, dopamine signaling, serotonin signaling, PSD-95, neurodevelopmental disorders
MeSH terms
Disks Large Homolog 4 Protein, Animals, Behavior, Animal, Brain, Postural Balance, Magnetic Resonance Imaging, Membrane Proteins, Motor Activity, Nervous System, Signal Transduction, Mice, Knockout, Neurotransmitter Agents, Reverse Transcriptase Polymerase Chain Reaction, Gait Ataxia, Intracellular Signaling Peptides and Proteins, Mice, Guanylate Kinases, Basic Helix-Loop-Helix Proteins

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