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Abnormal neurodevelopment, neurosignaling and behaviour in Npas3-deficient mice
Eric W Brunskill1, Lisa A Ehrman, Michael T Williams
1Division of Cardiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267, USA. eric.brunskill@uc.edu
The European Journal of Neuroscience
|September 30, 2005
Summary
Npas3 deficiency causes brain abnormalities and behavioral issues in mice. This gene is crucial for normal brain development and neurosignaling pathways, impacting neurotransmitter function.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Npas3 is a transcription factor belonging to the bHLH-PAS superfamily.
- It is broadly expressed in the developing neuroepithelium, suggesting a role in brain formation.
Purpose of the Study:
- To investigate the function of Npas3 in brain development and neurobehavior.
- To characterize the effects of Npas3 deficiency on neurosignaling pathways.
Main Methods:
- Generation and characterization of Npas3 knockout (Npas3-/-) mice.
- Behavioral assessments including locomotor activity, gait analysis, acoustic startle response, recognition memory, and anxiety-related behaviors.
- Pharmacological characterization of glutamate, dopamine, and serotonin signaling pathways.
- Analysis of cortical PSD-95 expression.
Main Results:
- Npas3-/- mice displayed growth retardation and significant brain abnormalities, including reduced anterior hippocampus size, corpus callosum hypoplasia, and ventricular enlargement.
- Behavioral deficits observed in Npas3-/- mice included hyperactivity, gait abnormalities, impaired prepulse inhibition, recognition memory deficits, and altered anxiety responses.
- Dysfunctional glutamate, dopamine, and serotonin neurotransmitter signaling were identified, along with altered cortical PSD-95 expression.
Conclusions:
- Npas3 plays a critical role in normal mammalian brain development.
- Npas3 is essential for regulating key neurosignaling pathways, including those involving glutamate, dopamine, and serotonin.
- Npas3 deficiency leads to a spectrum of neurodevelopmental and behavioral abnormalities.