biostudies-literatureAguilar CMedical Research CouncilRoyal SocietyWellcome TrustBiotechnology and Biological Sciences Research Council110170https://www.ebi.ac.uk/biostudies/studies/S-EPMC11225360biostudies-literatureUnknown27(7)Despite some evidence indicating diverse roles of whirlin in neurons, the functional corollary of whirlin gene function and behavior has not been investigated or broadly characterized. 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 (<i>head-bob</i>, <i>hb</i>) 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 <i>head-bob</i> with <i>whirler</i> mutant mice confirmed the <i>head-bob</i> mutation as functionally distinct with compound mutants having a mild-moderate heiSciencePleiotropic brain function of whirlin identified by a novel mutation.PMC11225360MC U142684175MC_PC_U127561112MC U142661184BB/X000567/1MC_UP_1503/2MC_UP_2201/2090532/Z/09/ZA410-53658G0900747 91070102892/Z/13/ZCorns LFPotter PKWells SSimon MWilliams JJohnson SLWilliams DGillard SStarbuck BAtkins GOliveri SConcas DKumar SBardhan TAguilar CBlake ABanks GMarcotti WSethi SKurapati RHaynes ARLad HVBains RSParker AHeise IMburu PHutchison MTateossian HVikhe PJeng JYfalsePleiotropic brain function of whirlin identified by a novel mutation.Despite some evidence indicating diverse roles of whirlin in neurons, the functional corollary of whirlin gene function and behavior has not been investigated or broadly characterized. 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 (<i>head-bob</i>, <i>hb</i>) 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 <i>head-bob</i> with <i>whirler</i> mutant mice confirmed the <i>head-bob</i> mutation as functionally distinct with compound mutants having a mild-moderate he2024-01-01T00:00:00Z2024 Jul2026-06-01T16:17:16.017Z2026-04-08T13:59:48.939ZS-EPMC112253603897496410.1016/j.isci.2024.110170