Otoancorin, An Inner Ear Protein Restricted to the Interface between the Apical Surface of Sensory Epithelia and Their Overlying Acellular Gels, Is Defective in Autosomal Recessive Deafness DFNB22

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 99; no. 9; pp. 6240 - 6245
• Main Authors: Zwaenepoel, Ingrid, Mustapha, Mirna, Leibovici, Michel, Verpy, Elisabeth, Goodyear, Richard, Liu, Xue Zhong, Nouaille, Sylvie, Nance, Walter E., Kanaan, Moien, Avraham, Karen B., Tekaia, Fredj, Loiselet, Jacques, Lathrop, Marc, Richardson, Guy, Petit, Christine
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 30.04.2002; National Acad Sciences; The National Academy of Sciences
• Subjects: Amino Acid Sequence; Animals; Biological Sciences; Cloning, Molecular; Cochlea; Complementary DNA; Deafness; DFNB22 gene; DNA Mutational Analysis; DNA, Complementary - metabolism; Ear, Inner - metabolism; Epithelial cells; Epithelium - metabolism; Exons; Female; Gels; Genetic Linkage; Genetic mutation; Genetics; Genotype; GPI-Linked Proteins; Hearing Disorders - genetics; Humans; Inner ear; Inner hair cells; Life Sciences; Male; membrane anchors; Membrane Proteins - biosynthesis; Membrane Proteins - physiology; Mesothelin; Mice; Microscopy, Electron; Microscopy, Fluorescence; Molecular Sequence Data; Mutation; OTOA gene; otoancorin; Outer hair cells; Pedigree; Reverse Transcriptase Polymerase Chain Reaction; Sequence Homology, Amino Acid; Tissue Distribution; Israel, Palestine
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.082515999

A 3,673-bp murine cDNA predicted to encode a glycosylphosphatidylinositol-anchored protein of 1,088 amino acids was isolated during a study aimed at identifying transcripts specifically expressed in the inner ear. This inner ear-specific protein, otoancorin, shares weak homology with megakaryocyte potentiating factor/mesothelin precursor. Otoancorin is located at the interface between the apical surface of the inner ear sensory epithelia and their overlying acellular gels. In the cochlea, otoancorin is detected at two attachment zones of the tectorial membrane, a permanent one along the top of the spiral limbus and a transient one on the surface of the developing greater epithelial ridge. In the vestibule, otoancorin is present on the apical surface of nonsensory cells, where they contact the otoconial membranes and cupulae. The identification of the mutation (IVS12+2T>C) in the corresponding gene OTOA in one consanguineous Palestinian family affected by nonsyndromic recessive deafness DFNB22 assigns an essential function to otoancorin. We propose that otoancorin ensures the attachment of the inner ear acellular gels to the apical surface of the underlying nonsensory cells.