Vestibular defects in head-tilt mice result from mutations in Nox3, encoding an NADPH oxidase

  1. Rainer Paffenholz1,
  2. Rebecca A. Bergstrom2,
  3. Francesca Pasutto1,
  4. Philipp Wabnitz1,
  5. Robert J. Munroe2,
  6. Wolfgang Jagla1,
  7. Ulrich Heinzmann3,
  8. Andreas Marquardt1,
  9. Armin Bareiss1,
  10. Jürgen Laufs1,
  11. Andreas Russ4,
  12. Gabriele Stumm1,
  13. John C. Schimenti2, and
  14. David E. Bergstrom2,5
  1. 1Ingenium Pharmaceuticals AG, D-82152 Martinsried, Germany; 2The Jackson Laboratory, Bar Harbor, Maine 04609 USA; 3GSF-National Research Center for Environmental Health, Institute of Pathology, 85764, Germany; 4Genetics Unit, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK

Abstract

The vestibular system of the inner ear is responsible for the perception of motion and gravity. Key elements of this organ are otoconia, tiny biomineral particles in the utricle and the saccule. In response to gravity or linear acceleration, otoconia deflect the stereocilia of the hair cells, thus transducing kinetic movements into sensorineural action potentials. Here, we present an allelic series of mutations at the otoconia-deficient head tilt (het) locus, affecting the gene for NADPH oxidase 3 (Nox3). This series of mutations identifies for the first time a protein with a clear enzymatic function as indispensable for otoconia morphogenesis.

Keywords

Footnotes

  • Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1172504.

  • 5 Corresponding author.

    5 E-MAIL deb{at}jax.org; FAX (207) 288-6078.

    • Accepted February 2, 2004.
    • Received November 26, 2003.
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