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CRYM mutations cause deafness through thyroid hormone binding properties in the fibrocytes of the cochlea
  1. A Oshima1,
  2. S Suzuki2,
  3. Y Takumi1,
  4. K Hashizume2,
  5. S Abe3,
  6. S Usami1
  1. 1Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan
  2. 2Department of Aging Medicine and Geriatrics, Institute on Aging and Adaptation, Shinshu University School of Medicine, Graduate School, Matsumoto, Japan
  3. 3Laboratory of Molecular Medicine, Human Genome Centre, Institute of Medical Science, University of Tokyo, Tokyo, Japan
  1. Correspondence to:
 Professor Shin-ichi Usami
 Department of Otorhinolaryngology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan; usami{at}hsp.md.shinshu-u.ac.jp

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.

  • μ-crystallin
  • Na
  • K-ATPase
  • 3,5,3′-triiodo-L-thyronine (T3)-binding protein (CTBP)
  • spiral ligament
  • deafness

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Footnotes

  • Conflicts of interest: none declared

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