Article
作者: Kumar, Saumya ; Blake, Andrew ; Parker, Andy ; Hutchison, Marie ; Concas, Danilo ; Marcotti, Walter ; Heise, Ines ; Mburu, Philomena ; Tateossian, Hilda ; Williams, Debbie ; Bains, Rasneer S ; Wells, Sara ; Starbuck, Becky ; Banks, Gareth ; Haynes, Andrew R ; Sethi, Siddharth ; Atkins, Gemma ; Simon, Michelle ; Potter, Paul K ; Kurapati, Ramakrishna ; Vikhe, Pratik ; Aguilar, Carlos ; Lad, Heena V ; Oliveri, Simona ; Williams, Jackie ; Bardhan, Tanaya ; Gillard, Simon ; Corns, Lara F ; Jeng, Jing-Yi ; Johnson, Stuart L
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 (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. Utilizing transgenics, we demonstrate rescue of the hyperactive phenotype and combined with the expression profiling data conclude whirlin plays an essential role in activity-related behaviors. These results highlight a pleiotropic role of whirlin within the brain and implicate alternative, central mediated pathways in its function.