Pleiotropic brain function of whirlin identified by a novel mutation
Carlos Aguilar1, Debbie Williams1,2, Ramakrishna Kurapati1
1MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus, Didcot, Oxfordshire OX11 0RD, UK.
Iscience
|July 8, 2024
Summary
A mutation in the whirlin gene causes head-bobbing and hyperactivity in mice, revealing its crucial role in brain activity-related behaviors and sensorineural hearing.
Area of Science:
- Neuroscience
- Genetics
- Auditory Science
Background:
- The diverse roles of whirlin in neurons are not fully understood.
- Whirlin is critical for sensorineural hearing function.
Purpose of the Study:
- To investigate the function and behavior associated with whirlin gene.
- To characterize the impact of a novel whirlin mutation on mouse behavior and hearing.
Main Methods:
- Recessive ENU-mutagenesis screen to identify a whirlin splice-site mutation (head-bob, hb).
- Phenotyping tests to assess behavior (head-bobbing, hyperactivity) and hearing in mutant mice.
- Complementation tests with whirler mutants and transgenic rescue experiments.
Main Results:
- The head-bob mutation caused partial intron retention, frameshift, and premature termination codon in whirlin.
- Mutant mice exhibited head-bobbing and significant hyperactivity.
- Compound mutants showed mild-moderate hearing defects, confirming functional distinction.
- Transgenic rescue ameliorated the hyperactive phenotype.
Conclusions:
- Whirlin plays an essential role in activity-related behaviors, indicating a pleiotropic role in the brain.
- Central mediated pathways are implicated in whirlin's function.
- This study expands understanding of whirlin's function beyond auditory pathways.
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