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Mol. Cell. Biol. doi:10.1128/MCB.01282-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Mosaic complementation demonstrates a regulatory role for myosin VIIa in stereocilia actin dynamics

Mouse Genomics and Genetics of Deafness laboratories, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK

^* To whom correspondence should be addressed. Email: hmp{at}sanger.ac.uk.

	Abstract

We have developed a BAC transgenesis approach that allowed expression of myosin VIIa from the mouse X-chromosome. We demonstrated complementation of the Myo7a null mutant phenotype producing a fine mosaic of two types of sensory hair cells within inner ear epithelia of hemizygous transgenic females due to X-inactivation. Direct comparison between neighboring auditory hair cells different only with respect to myosin VIIa expression revealed that mutant stereocilia are significantly longer than their complemented counterparts. Myosin VIIa-deficient hair cells showed an abnormally persistent stereocilia tip localization of whirlin, a protein directly linked to stereocilia elongation. Furthermore, myosin VIIa localized at the tips of all abnormally short stereocilia of mice deficient for either myosin XVa or whirlin. Our results strongly suggest that myosin VIIa regulates the establishment of a set-point for stereocilia heights, and this novel role may influence their normal staircase-like arrangement within a bundle.

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