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Published on: May 12, 2015
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A Upf3b-mutant mouse model with behavioral and neurogenesis defects.
L Huang1, E Y Shum1, S H Jones1
1Department of Reproductive Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
Molecular Psychiatry
|September 27, 2017
Summary
Nonsense-mediated RNA decay (NMD) factor UPF3B is crucial for brain development. Loss of UPF3B in mice impairs learning, sensorimotor gating, and neural stem cell differentiation, offering a model for neurodevelopmental disorders.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Nonsense-mediated RNA decay (NMD) is a conserved RNA surveillance pathway.
- NMD is developmentally regulated and influences organismal development.
- UPF3B mutations are linked to human neurodevelopmental disorders like intellectual disability (ID), autism spectrum disorder (ASD), and schizophrenia (SCZ).
Purpose of the Study:
- To investigate the role of UPF3B in neurodevelopment using a mouse model.
- To characterize the behavioral and cellular phenotypes of Upf3b-null mice.
- To identify UPF3B-regulated genes in the brain.
Main Methods:
- Generation and characterization of Upf3b-null mice.
- Behavioral testing including fear conditioning and prepulse inhibition (PPI).
- In vivo analysis of dendritic spine maturation and neural stem cell differentiation.
- RNA sequencing (RNAseq) of frontal cortex tissue.
Main Results:
- Upf3b-null mice exhibit deficits in fear-conditioned learning and PPI.
- Cortical pyramidal neurons show impaired dendritic spine maturation.
- Neural stem cells display defective differentiation.
- RNAseq identified UPF3B-regulated transcripts involved in neural development and disease.
Conclusions:
- Upf3b-null mice represent a valuable model for studying ID and neurodevelopmental disorders.
- UPF3B plays a critical role in learning, sensorimotor gating, and neural development.
- Defects in UPF3B function contribute to the pathophysiology of neurodevelopmental conditions.
