TY - JOUR
T1 - Mutations in Cdh23 cause nonsyndromic hearing loss in waltzer mice
AU - Wilson, Scott M.
AU - Householder, Deborah B.
AU - Coppola, Vincenzo
AU - Tessarollo, Lino
AU - Fritzsch, Bernd
AU - Lee, E. Chiang
AU - Goss, Dee
AU - Carlson, George A.
AU - Copeland, Neal G.
AU - Jenkins, Nancy A.
N1 - Funding Information:
This research was supported by the National Cancer Institute, Department of Health and Human Services (N.G.C., N.A.J., and L.T.) No. 2 P01 DC00215 (B.F.) and NS22786 (G.A.C.). We thank Keith Rogers and Jennifer Matta from the Histotechnology Laboratory for tissue preparation and sectioning. We also thank Fran Dorsey, Joanne Deitz, and Debbie Swing for expert mouse assistance. We also thank Julie Wilson for her help with the manuscript.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2001/6/1
Y1 - 2001/6/1
N2 - Mutations at the waltzer (v) locus result in deafness and vestibular dysfunction due to degeneration of the neuroepithelium within the inner ear. Here, we use a positional cloning approach to show that waltzer encodes a novel cadherin (Cdh23), which is most closely related to the Drosophila Fat protein. A single nucleotide deletion in the vJ allele and a single nucleotide insertion in the v allele are predicted to truncate each protein near the N-terminus and produce a functional null allele. In situ hybridization analysis showed that Cdh23 is expressed in the sensory hair cells of the inner ear, where it has been suggested to be a molecule critical for crosslinking of the stereocilia. In addition, Cdh23 is expressed in the urticulo-saccular foramen, the ductus reuniens, and Reissner's membrane, suggesting that Cdh23 may also be involved in maintaining the ionic composition of the endolymph. Finally, mutations in human CDH23 have recently been described for two loci, DFNB12 and USH1D, which cause nonsyndromic deafness, identifying waltzer as a mouse model for human hearing loss.
AB - Mutations at the waltzer (v) locus result in deafness and vestibular dysfunction due to degeneration of the neuroepithelium within the inner ear. Here, we use a positional cloning approach to show that waltzer encodes a novel cadherin (Cdh23), which is most closely related to the Drosophila Fat protein. A single nucleotide deletion in the vJ allele and a single nucleotide insertion in the v allele are predicted to truncate each protein near the N-terminus and produce a functional null allele. In situ hybridization analysis showed that Cdh23 is expressed in the sensory hair cells of the inner ear, where it has been suggested to be a molecule critical for crosslinking of the stereocilia. In addition, Cdh23 is expressed in the urticulo-saccular foramen, the ductus reuniens, and Reissner's membrane, suggesting that Cdh23 may also be involved in maintaining the ionic composition of the endolymph. Finally, mutations in human CDH23 have recently been described for two loci, DFNB12 and USH1D, which cause nonsyndromic deafness, identifying waltzer as a mouse model for human hearing loss.
UR - http://www.scopus.com/inward/record.url?scp=0035366320&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035366320&partnerID=8YFLogxK
U2 - 10.1006/geno.2001.6554
DO - 10.1006/geno.2001.6554
M3 - Article
C2 - 11386759
AN - SCOPUS:0035366320
VL - 74
SP - 228
EP - 233
JO - Genomics
JF - Genomics
SN - 0888-7543
IS - 2
ER -