CRYM mutations cause deafness through thyroid hormone binding properties in the fibrocytes of the cochlea

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Abstract
Background: In a search for mutations of μ-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. Objective: To investigate the mechanism of hearing loss caused by CRYM mutations Methods: T3 binding activity of mutant μ-crystallin was compared with that of wild-type μ-crystallin, because μ-crystallin is known to be identical to T3 binding protein. To explore the sites within the cochlea where μ-crystallin is functioning, its localisation in the mouse cochlea was investigated immunocytochemically using a specific antibody. Results: 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 μ-crystallin was distributed within type II fibrocytes of the lateral wall, which are known to contain Na,K-ATPase. Conclusions:CRYM mutations may cause auditory dysfunction through thyroid hormone binding effects on the fibrocytes of the cochlea. μ-Crystallin may be involved in the potassium ion recycling system together with Na,K-ATPase. Future animal experiments will be necessary to confirm a causal relation between Na,K-ATPase, T3, and deafness.

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