The research for inner ear specific proteins and deafness gene coding proteins.

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Through cDNA microarray analysis of gene expression in the cochlea and vestibule, a number of genes that are highly expressed specifically in auditory tissues have been detected (Abe et al., 2003). Moreover, screening for genetic alterations in these genes has identified several possible disease-causing mutations. Here we targeted the COL9A3 (type IX collagen), mu-crystallin (CRYM) and ubiquitin A-52 residue ribosomal protein fusion product 1 (UbA52) genes that are highly expressed specifically in the cochlea and vestibule. The localization of the proteins coded by these genes and the mechanism of hearing disorders were examined in the inner ear.Immunocytochemical analysis revealed that type IX collagen is distributed in the tectorial membrane of the organ of Corti. To confirm the significance of type IX collagen for normal hearing, we assessed the detailed morphological and electrophysiological features of type IX collagen knock-out mice, which have recently been reported as a deafnes … More s model. Through assessment by auditory brainstem response (ABR), knock-out mice were shown to have progressive hearing loss.In a search for mutations of mu-crystallin (CRYM), a taxion specific crystalline which is also known as an NADP regulated thyroid hormone binding protein, two mutations were found at the C-terminus in patients with non-syndromic deafness. T3 binding activity of mutant mu-crystallin was compared with that of wild-type mu-crystallin, and one mutant was shown to have no binding capacity for T3, indicating that CRYM mutations cause auditory dysfunction through thyroid hormone binding properties. Immunocytochemical results indicated that mu-crystallin was co-localized with Na,K-ATPase within type II fibrocytes of the lateral wall. Therefore, CRYM mutations may cause auditory dysfunction through thyroid hormone binding effects on the fibrocytes of the cochlea. mu-Crystallin may be involved in the potassium ion recycling system together with Na,K-ATPase.The ubiquitin A-52 residue ribosomal protein fusion product 1 (UbA52) was found by immunocytochemical investigation to be distributed in the strial marginal cells and vestibular dark cells, which regulate the endolymphatic ion homeostasis. In the developing mouse cochlea, no significant staining was observed from birth to postnatal day 3, whereas after postnatal day 6, strong UbA52-immunoreactivities were observed in strial marginal cells. Endolymphatic K + concentration is elevated between postnatal days 3-8, therefore, our results indicate that UbA52 may have a functional role in regulation of ion secretion in the inner ear. Less