| First Author | Ebrahim S | Year | 2016 |
| Journal | Cell Rep | Volume | 15 |
| Issue | 5 | Pages | 935-943 |
| PubMed ID | 27117407 | Mgi Jnum | J:235390 |
| Mgi Id | MGI:5796227 | Doi | 10.1016/j.celrep.2016.03.081 |
| Citation | Ebrahim S, et al. (2016) Alternative Splice Forms Influence Functions of Whirlin in Mechanosensory Hair Cell Stereocilia. Cell Rep 15(5):935-43 |
| abstractText | WHRN (DFNB31) mutations cause diverse hearing disorders: profound deafness (DFNB31) or variable hearing loss in Usher syndrome type II. The known role of WHRN in stereocilia elongation does not explain these different pathophysiologies. Using spontaneous and targeted Whrn mutants, we show that the major long (WHRN-L) and short (WHRN-S) isoforms of WHRN have distinct localizations within stereocilia and also across hair cell types. Lack of both isoforms causes abnormally short stereocilia and profound deafness and vestibular dysfunction. WHRN-S expression, however, is sufficient to maintain stereocilia bundle morphology and function in a subset of hair cells, resulting in some auditory response and no overt vestibular dysfunction. WHRN-S interacts with EPS8, and both are required at stereocilia tips for normal length regulation. WHRN-L localizes midway along the shorter stereocilia, at the level of inter-stereociliary links. We propose that differential isoform expression underlies the variable auditory and vestibular phenotypes associated with WHRN mutations. |
