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


OBJECTIVE
To investigate the mechanism of hearing loss caused by CRYM mutations


METHODS
T3 binding activity of mutant mu-crystallin was compared with that of wild-type mu-crystallin, because mu-crystallin is known to be identical to T3 binding protein. To explore the sites within the cochlea where mu-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 mu-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. mu-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.
Oshima
A
A
Suzuki
S
S
Takumi
Y
Y
Hashizume
K
K
Abe
S
S
Usami
S
S
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D003051:Cochlea / Q000166:cytology / Q000378:metabolism*; D003459:Crystallins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D003638:Deafness / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D020125:Mutation, Missense; D021122:Protein Subunits / Q000032:analysis / Q000378:metabolism; D012156:Reticulocytes / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism*; D000090803:mu-Crystallins; D000097810:Thyroid Hormone-Binding Proteins
D002352:Carrier Proteins; D003459:Crystallins; D008565:Membrane Proteins; D021122:Protein Subunits; D000254:Sodium-Potassium-Exchanging ATPase; D013963:Thyroid Hormones; D014284:Triiodothyronine; D000090803:mu-Crystallins; D000097810:Thyroid Hormone-Binding Proteins; C000716469:CRYM protein, human; C000716470:Crym protein, mouse