| First Author | Aguilar C | Year | 2024 |
| Journal | iScience | Volume | 27 |
| Issue | 7 | Pages | 110170 |
| PubMed ID | 38974964 | Mgi Jnum | J:351467 |
| Mgi Id | MGI:7702972 | Doi | 10.1016/j.isci.2024.110170 |
| Citation | Aguilar C, et al. (2024) Pleiotropic brain function of whirlin identified by a novel mutation. iScience 27(7):110170 |
| abstractText | 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. |
