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  Loss of the mammal-specific tectorial membrane component CEA cell adhesion molecule 16 (CEACAM16) leads to hearing impairment at low and high frequencies

Kammerer, R., Rüttiger, L., Riesenberg, R., Schäuble, C., Krupar, R., Kamp, A., et al. (2012). Loss of the mammal-specific tectorial membrane component CEA cell adhesion molecule 16 (CEACAM16) leads to hearing impairment at low and high frequencies. Journal of Biological Chemistry, 287, 21584-21598.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-B8A3-4 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-B8A4-2
Genre: Journal Article

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Kammerer, Robert1, Author
Rüttiger, Lukas2, Author
Riesenberg, Rainer3, Author
Schäuble, Constanze3, Author
Krupar, Rosemarie3, Author
Kamp, Annegret3, Author
Sunami, Kishiko 4, Author
Eisenried, Andreas3, Author
Hennenberg, Martin5, Author
Grunert, Fritz6, Author
Breß, Andreas2, Author
Battaglia, Sebastiano7, Author              
Schrewe, Heinrich7, Author              
Knipper, Marlies2, Author
Schneider, Marlon R.8, Author
Affiliations:
1Instute of Immunology, Friedrich-Loeffler Institut, Greifswald-Insel Riems, Germany, ou_persistent22              
2Department of Otorhinolaryngology, University of Tübingen, Hearing Research Centre Tübingen, Tübingen, Germany, ou_persistent22              
3Tumor Immunology Laboratory, LIFE Center, University Clinic of Munich, Munich, Germany, ou_persistent22              
4Department of Otolaryngology, Osaka City University Medical School, Osaka, Japan, ou_persistent22              
5Experimental Urology, Department of Urology, University Clinic of Munich, Munich, Germany, ou_persistent22              
6Aldevron Freiburg, Freiburg, Germany, ou_persistent22              
7Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society, Ihnestr. 73, 14195 Berlin, ou_1433548              
8Institute of Molecular Animal Breeding and Biotechnology, Gene Center, University of Munich, Munich, Germany, ou_persistent22              

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 Abstract: The vertebrate-restricted carcinoembryonic antigen gene family evolves extremely rapidly. Among their widely expressed members, the mammal-specific, secreted CEACAM16 is exceptionally well conserved and specifically expressed in the inner ear. To elucidate a potential auditory function we inactivated murine Ceacam16 by homologous recombination. In young Ceacam16-/- mice the hearing threshold for frequencies below 10 kHz and above 22 kHz was raised. This hearing impairment progressed with age. A similar phenotype is observed in hearing-impaired members of Family 1070 with non-syndromic autosomal dominant hearing loss (DFNA4) who carry a missense mutation in CEACAM16. CEACAM16 was found in interdental and Deiters cells and was deposited in the tectorial membrane of the cochlea between postnatal day 12 and 15, when hearing starts in mice. In cochlear sections of Ceacam16-/- mice tectorial membranes were significantly more often stretched out as compared to wild-type mice where they were mostly contracted and detached from the outer hair cells. Homotypic cell sorting observed after ectopic cell surface expression of the carboxy-terminal immunoglobulin variable-like N2 domain of CEACAM16 indicated that CEACAM16 can interact in trans. Furthermore, Western blot analyses of membrane-bound CEACAM16 under reducing and non-reducing conditions demonstrated oligomerization via unpaired cysteines. Taken together, CEACAM16 probably can form higher order structures with other tectorial membrane proteins such as α-tectorin and β-tectorin and influences the physical properties of the tectorial membrane. Evolution of CEACAM16 might have been an important step for the specialization of the mammalian cochlea allowing hearing over an extended frequency range.

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Language(s): eng - English
 Dates: 2012-04-27
 Publication Status: Published online
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Title: Journal of Biological Chemistry
  Other : J. Biol. Chem.
Source Genre: Journal
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Publ. Info: Baltimore, etc. : American Society for Biochemistry and Molecular Biology [etc.]
Pages: - Volume / Issue: 287 Sequence Number: - Start / End Page: 21584 - 21598 Identifier: ISSN: 0021-9258
CoNE: https://pure.mpg.de/cone/journals/resource/954925410826