Despite some evidence indicating diverse roles of whirlin in neurons, the functional corollary of whirlin gene function and behaviour has not been investigated or broadly characterised. A single nucleotide variant was identified from our recessive ENU-mutagenesis screen at a donor-splice site in whirlin, a protein critical for proper sensorineural hearing function. The mutation (head-bob, hb) led to partial intron-retention causing a frameshift and introducing a premature termination codon. Mutant mice had a head-bobbing phenotype and significant hyperactivity across several phenotyping tests. Lack of complementation of head-bob with whirler mutant mice confirmed the head-bob mutation as functionally distinct with compound mutants having a mild-moderate hearing defect. Utilising transgenics, we demonstrate rescue of the hyperactive phenotype and combined with the expression profiling data conclude whirlin plays an essential role in activity-related behaviours. These results highlight a pleiotropic role of whirlin within the brain and implicates alternative, central mediated pathways in its function.
Aguilar, CarlosWilliams, DebbieKurapati, RamakrishnaBains, Rasneer S.Mburu, PhilomenaParker, AndyWilliams, JackieConcas, DaniloTateossian, HildaHaynes, Andrew R.Banks, GarethVikhe, PratikHeise, InesHutchison, MarieAtkins, GemmaGillard, SimonStarbuck, BeckyOliveri, SimonaBlake, AndrewSethi, SiddharthKumar, SaumyaBardhan, TanayaJeng Jing-YiJohnson, Stuart L.Corns, Lara F.Marcotti, WalterSimon, MichelleWells, SaraPotter, Paul K. Lad, Heena V.
Department of Biological and Medical Sciences
Year of publication: 2024Date of RADAR deposit: 2024-06-07