TY - JOUR
T1 - The Coxsackievirus and Adenovirus Receptor
T2 - A new adhesion protein in cochlear development
AU - Excoffon, Katherine J.D.A.
AU - Avenarius, Matthew R.
AU - Hansen, Marlan R.
AU - Kimberling, William J.
AU - Najmabadi, Hossein
AU - Smith, Richard J.H.
AU - Zabner, Joseph
N1 - Funding Information:
We thank Jamie Kesselring for assistance with manuscript preparation, Michael Welsh for discussions, Tom Moninger, Geri Traver, Nick Gansemer, the Central Microscopy Research Facility, the Gene Transfer Vector Core, the Gene Transfer Morphology Core (supported by the NIDDK [DK54759] and the Cystic Fibrosis Foundation, ENGELH98S0), the Hybridoma/Tissue Culture Facility, the In Vitro Cell Models Core (supported by the National Heart, Lung and Blood Institute and the National Institutes of Diabetes and Digestive and Kidney Diseases [DK54759]). KE is supported by a fellowship from the Parker B. Francis Foundation (PBF). This work was supported by a PPG grant from the NIH (HL51670-11), a grant from the NIDCD (R01-DC02842) to RJHS, and a grant from the Iran Deputy of Research and Technology, Ministry of Health and Medical Education (P 6176) to HN.
PY - 2006/5
Y1 - 2006/5
N2 - The Coxsackievirus and Adenovirus Receptor (CAR) is an essential regulator of cell growth and adhesion during development. The gene for CAR, CXADR, is located within the genomic locus for Usher syndrome type 1E (USH1E). Based on this and a physical interaction with harmonin, the protein responsible for USH1C, we hypothesized that CAR may be involved in cochlear development and that mutations in CXADR may be responsible for USH1E. The expression of CAR in the cochlea was determined by PCR and immunofluorescence microscopy. We found that CAR expression is highly regulated during development. In neonatal mice, CAR is localized to the junctions of most cochlear cell types but is restricted to the supporting and strial cells in adult cochlea. A screen of two populations consisting of non-syndromic deaf and Usher 1 patients for mutations in CXADR revealed one haploid mutation (P356S). Cell surface expression, viral receptor activity, and localization of the mutant form of CAR were indistinguishable from wild-type CAR. Although we were unable to confirm a role for CAR in autosomal recessive, non-syndromic deafness, or Usher syndrome type 1, based on its regulation, localization, and molecular interactions, CAR remains an attractive candidate for genetic deafness.
AB - The Coxsackievirus and Adenovirus Receptor (CAR) is an essential regulator of cell growth and adhesion during development. The gene for CAR, CXADR, is located within the genomic locus for Usher syndrome type 1E (USH1E). Based on this and a physical interaction with harmonin, the protein responsible for USH1C, we hypothesized that CAR may be involved in cochlear development and that mutations in CXADR may be responsible for USH1E. The expression of CAR in the cochlea was determined by PCR and immunofluorescence microscopy. We found that CAR expression is highly regulated during development. In neonatal mice, CAR is localized to the junctions of most cochlear cell types but is restricted to the supporting and strial cells in adult cochlea. A screen of two populations consisting of non-syndromic deaf and Usher 1 patients for mutations in CXADR revealed one haploid mutation (P356S). Cell surface expression, viral receptor activity, and localization of the mutant form of CAR were indistinguishable from wild-type CAR. Although we were unable to confirm a role for CAR in autosomal recessive, non-syndromic deafness, or Usher syndrome type 1, based on its regulation, localization, and molecular interactions, CAR remains an attractive candidate for genetic deafness.
KW - CAR
KW - CXADR
KW - Cochlea
KW - Coxsackievirus and Adenovirus Receptor
KW - Deafness
KW - Usher syndrome
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U2 - 10.1016/j.heares.2006.02.009
DO - 10.1016/j.heares.2006.02.009
M3 - Article
C2 - 16678988
AN - SCOPUS:33646231744
SN - 0378-5955
VL - 215
SP - 1
EP - 9
JO - Hearing Research
JF - Hearing Research
IS - 1-2
ER -