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Mosaic Complementation Demonstrates a Regulatory Role for Myosin VIIa in Actin Dynamics of Stereocilia ^,

Haydn M. Prosser,^1,* Agnieszka K. Rzadzinska,^2, Karen P. Steel,² and Allan Bradley¹

Mouse Genomics,¹ Genetics of Deafness Laboratories, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom²

Received 17 July 2007/ Returned for modification 29 August 2007/ Accepted 15 December 2007

We have developed a bacterial artificial chromosome transgenesis approach that allowed the expression of myosin VIIa from the mouse X chromosome. We demonstrated the 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 comparisons between neighboring auditory hair cells that were different only with respect to myosin VIIa expression revealed that mutant stereocilia are significantly longer than those of their complemented counterparts. Myosin VIIa-deficient hair cells showed an abnormally persistent tip localization of whirlin, a protein directly linked to elongation of stereocilia, in stereocilia. 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 setpoint for stereocilium heights, and this novel role may influence their normal staircase-like arrangement within a bundle.

Published ahead of print on 26 December 2007.

Supplemental material for this article may be found at http://mcb.asm.org/.

H.M.P. and A.K.R. contributed equally to this article.

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