CRYM mutations cause deafness through thyroid hormone binding properties in the fibrocytes of the cochlea
- 1Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan
- 2Department of Aging Medicine and Geriatrics, Institute on Aging and Adaptation, Shinshu University School of Medicine, Graduate School, Matsumoto, Japan
- 3Laboratory of Molecular Medicine, Human Genome Centre, Institute of Medical Science, University of Tokyo, Tokyo, Japan
- Correspondence to: Professor Shin-ichi Usami Department of Otorhinolaryngology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan;
- Received 28 April 2005
- Accepted 22 June 2005
- Revised 11 June 2005
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.
- 3,5,3′-triiodo-L-thyronine (T3)-binding protein (CTBP)
- spiral ligament
Conflicts of interest: none declared