Human Molecular Genetics Advance Access originally published online on September 30, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Human Molecular Genetics, 2003, Vol. 12, No. 23 3075-3086
DOI: 10.1093/hmg/ddg332
© 2003 Oxford University Press
Mouse models of USH1C and DFNB18: phenotypic and molecular analyses of two new spontaneous mutations of the Ush1c gene
The Jackson Laboratory, Bar Harbor, ME 04609, USA
Received July 14, 2003; Revised September 15, 2003; Accepted September 23, 2003
We mapped two new recessive mutations causing circling behavior and deafness to the same region on chromosome 7 and showed they are allelic by complementation analysis. One was named ‘deaf circler’ (allele symbol dfcr) and the other ‘deaf circler 2 Jackson’ (allele symbol dfcr-2J). Both were shown to be mutations of the Ush1c gene, the mouse ortholog of the gene responsible for human Usher syndrome type IC and for the non-syndromic deafness disorder DFNB18. The Ush1c gene contains 28 exons, 20 that are constitutive and eight that are alternatively spliced. The dfcr mutation is a 12.8 kb intragenic deletion that eliminates three constitutive and five alternatively spliced exons. The dfcr-2J mutation is a 1 bp deletion in an alternatively spliced exon that creates a transcriptional frame shift, changing 38 amino acid codons before introducing a premature stop codon. Both mutations cause congenital deafness and severe balance deficits due to inner ear dysfunction. The stereocilia of cochlear hair cells are disorganized and splayed in mutant mice, with subsequent degeneration of the hair cells and spiral ganglion cells. Harmonin, the protein encoded by Ush1c, has been shown to bind, by means of its PDZ-domains, with the products of other Usher syndrome genes, including Myo7a, Cdh23 and Sans. The complexes formed by these protein interactions are thought to be essential for maintaining the integrity of hair cell stereocilia. The Ush1c mutant mice described here provide a means to directly investigate these interactions in vivo and to evaluate gene structure–function relationships that affect inner ear and eye phenotypes.
* To whom correspondence should be addressed. Tel: +1 2072886228; Fax: +1 2072886149; Email: krj{at}jax.org
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  G. Lefevre, V. Michel, D. Weil, L. Lepelletier, E. Bizard, U. Wolfrum, J.-P. Hardelin, and C. Petit A core cochlear phenotype in USH1 mouse mutants implicates fibrous links of the hair bundle in its cohesion, orientation and differential growth Development, April 15, 2008; 135(8): 1427 - 1437. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Liu, O. V. Bulgakov, K. N. Darrow, B. Pawlyk, M. Adamian, M. C. Liberman, and T. Li Usherin is required for maintenance of retinal photoreceptors and normal development of cochlear hair cells PNAS, March 13, 2007; 104(11): 4413 - 4418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. H. Gagnon, C. M. Longo-Guess, M. Berryman, J.-B. Shin, K. W. Saylor, H. Yu, P. G. Gillespie, and K. R. Johnson The Chloride Intracellular Channel Protein CLIC5 Is Expressed at High Levels in Hair Cell Stereocilia and Is Essential for Normal Inner Ear Function J. Neurosci., October 4, 2006; 26(40): 10188 - 10198. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. L. Haywood-Watson II, Z. M. Ahmed, S. Kjellstrom, R. A. Bush, Y. Takada, L. L. Hampton, J. F. Battey, P. A. Sieving, and T. B. Friedman Ames waltzer deaf mice have reduced electroretinogram amplitudes and complex alternative splicing of pcdh15 transcripts. Invest. Ophthalmol. Vis. Sci., July 1, 2006; 47(7): 3074 - 3084. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Adato, G. Lefevre, B. Delprat, V. Michel, N. Michalski, S. Chardenoux, D. Weil, A. El-Amraoui, and C. Petit Usherin, the defective protein in Usher syndrome type IIA, is likely to be a component of interstereocilia ankle links in the inner ear sensory cells Hum. Mol. Genet., December 15, 2005; 14(24): 3921 - 3932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Longo-Guess, L. H. Gagnon, S. A. Cook, J. Wu, Q. Y. Zheng, and K. R. Johnson A missense mutation in the previously undescribed gene Tmhs underlies deafness in hurry-scurry (hscy) mice PNAS, May 31, 2005; 102(22): 7894 - 7899. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Adato, V. Michel, Y. Kikkawa, J. Reiners, K. N. Alagramam, D. Weil, H. Yonekawa, U. Wolfrum, A. El-Amraoui, and C. Petit Interactions in the network of Usher syndrome type 1 proteins Hum. Mol. Genet., February 1, 2005; 14(3): 347 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Y. Zheng, D. Yan, X. M. Ouyang, L. L. Du, H. Yu, B. Chang, K. R. Johnson, and X. Z. Liu Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans Hum. Mol. Genet., January 1, 2005; 14(1): 103 - 111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Hawkins and M. Lovett The developmental genetics of auditory hair cells Hum. Mol. Genet., October 1, 2004; 13(suppl_2): R289 - R296. [Abstract] [Full Text] [PDF]
|
|