Behavioral and regulatory abnormalities in mice deficient in the NPAS1 and NPAS3 transcription factors
Open accessAbstract
Laboratory mice bearing inactivating mutations in the genes encoding the NPAS1 and NPAS3 transcription factors have been shown to exhibit a spectrum of behavioral and neurochemical abnormalities. Behavioral abnormalities included diminished startle response, as measured by prepulse inhibition, and impaired social recognition. NPAS1/NPAS3-deficient mice also exhibited stereotypic darting behavior at weaning and increased locomotor activity. Immunohistochemical staining assays showed that the NPAS1 and NPAS3 proteins are expressed in inhibitory interneurons and that the viability and anatomical distribution of these neurons are unaffected by the absence of either transcription factor. Adult brain tissues from NPAS3- and NPAS1/NPAS3-deficient mice exhibited a distinct reduction in reelin, a large, secreted protein whose expression has been reported to be attenuated in the postmortem brain tissue of patients with schizophrenia. These observations raise the possibility that a regulatory program controlled in inhibitory interneurons by the NPAS1 and NPAS3 transcription factors may be either substantively or tangentially relevant to psychosis.
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Npas3 plays an important role during brain development, specifically in the control of neurosignaling pathways, and is involved in astrogenesis.
“Analysis of Npas3 deficient mice (Npas3−/−) showed that this protein plays an important role during brain development, specifically in the control of neurosignaling pathways (Erbel-Sieler et al. 2004; Brunskill et al. 2005), and it was also involved in astrogenesis (Li et al. 2022).”
From The Human Accelerated Region HAR202 Controls <i>NPAS3</i> Expression in the Developing Forebrain Displaying Differential Enhancer Activity Between Modern and Archaic Human Sequences (2024) · cites this paper as Erbel-Sieler et al. 2004
The Results report reduced reelin expression in NPAS3-deficient mice, and the Discussion speculates that NPAS3 controls regulatory pathways in inhibitory interneurons. The Discussion describes reelin’s role in embryonic brain patterning, but does not establish that NPAS3 itself has an important role during brain development; its pathway-control claim is also tentative. Astrogenesis is attributed to Li et al. (2022), not to this source. (LLM, conf=0.86)
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“Analysis of Npas3 deficient mice ( Npas3 − / − ) showed that this protein plays an important role during brain development, specifically in the control of neurosignaling pathways (Erbel-Sieler et al. 2004; Brunskill et al. 2005), and it was also involved in astrogenesis (Li et al. 2022).”
Background
- Authors
- Erbel-Sieler, C., Dudley, C., Zhou, Y., Wu, X., Estill, S. J., Han, T., Diaz-Arrastia, R., Brunskill, E. W., Potter, S. S., & McKnight, S. L.
- Affiliations
- University of Cincinnati (US)
- University of Mississippi (US)
- Cincinnati Children's Hospital Medical Center (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2004-09-03
- Volume
- 101
- Issue
- 37
- Pages
- 13648-13653
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC518807
- OpenAlex
- W2051905619
- Cited by
- 178
- References
- 20
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 6 · 2023: 4 · 2022: 5 · 2021: 10 · 2020: 5 · 2019: 4 · 2018: 5 · 2017: 6 · 2016: 10 · 2015: 9 · 2014: 7 · 2013: 10 · 2012: 9
- FWCI
- 6.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- McKnight Foundation
- University of Texas Southwestern Medical Center
- National Institute of Mental Health (R37MH059388)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- NPAS3, transcription factors, prepulse inhibition, startle response, social recognition, locomotor activity, inhibitory interneurons, reelin, schizophrenia, psychosis, knockout mice
- MeSH terms
- Reelin Protein, Aging, Animals, Behavior, Animal, Brain, gamma-Aminobutyric Acid, Homozygote, Nerve Tissue Proteins, Neurons, Serine Endopeptidases, Social Behavior, Transcription Factors, Cell Adhesion Molecules, Neuronal, Extracellular Matrix Proteins, Gene Deletion, Mice, Knockout, Gene Expression Profiling, Mice, Basic Helix-Loop-Helix Proteins, Basic Helix-Loop-Helix Transcription Factors
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