TY - JOUR
T1 - Longitudinal gradients of KCNQ4 expression in spiral ganglion and cochlear hair cells correlate with progressive hearing loss in DFNA2
AU - Beisel, Kirk W.
AU - Nelson, Nathan C.
AU - Delimont, Duane C.
AU - Fritzsch, Bernd
N1 - Funding Information:
We thank Drs. Ruth Anne Eatock, Shelley Smith, and Zoreh Talebizadeh for helpful discussions and suggestions, and Dr. Eatock for evaluation and critical review of this manuscript. This investigation was supported by research grants from the USPHS National Institute on Deafness and Other Communication Disorders grants R01 DC02041 (K.W.B.), R01 DC01813 (K.W.B.) and 2 P01 DC00215-14A1 (B.F.) and the National Organization for Hearing Research (B.F.).
Copyright:
Copyright 2006 Elsevier B.V., All rights reserved.
PY - 2000/10/20
Y1 - 2000/10/20
N2 - Mutations in the human KCNQ4 gene were recently found by Kubisch et al. [Cell 96 (1999) 437-446] to cause a non-syndromic, autosomal dominant, progressive hearing loss, DFNA2. The mouse Kcnq4 orthologue was previously localized to the outer hair cells (OHCs) of the inner ear, suggesting the pathophysiological effects were due to dysfunctional OHCs. Yet, OHC dysfunction does not provide a plausible explanation for the progressive nature of the frequency specific hearing loss. We have re-examined and extended the expression analyses of KCNQ4 in the murine inner ear using RT-PCR and whole mount in situ hybridization. Our results confirmed that the rat KCNQ4 orthologue is expressed in both inner and outer hair cells. Reciprocal longitudinal gradients were found in inner hair cells (IHCs) and OHCs. The strongest expression of KCNQ4 in IHCc was in the base of the cochlea and in the apex for OHCs. Similar to the IHCs, a basal to apical gradient was present in the spiral sensory neurons. IHCs mediate hearing via their afferent sensory neurons, whereas OHCs function as active cochlear amplifiers. The complete absence of OHCs leads only to severe sensitivity reduction, but not complete hearing loss. Our data suggest that the primary defect leading to initial high frequency loss and subsequent progressive hearing loss for all frequencies may be due to spiral ganglion and/or IHC dysfunction, rather than an OHC aberration. (C) 2000 Elsevier Science B.V.
AB - Mutations in the human KCNQ4 gene were recently found by Kubisch et al. [Cell 96 (1999) 437-446] to cause a non-syndromic, autosomal dominant, progressive hearing loss, DFNA2. The mouse Kcnq4 orthologue was previously localized to the outer hair cells (OHCs) of the inner ear, suggesting the pathophysiological effects were due to dysfunctional OHCs. Yet, OHC dysfunction does not provide a plausible explanation for the progressive nature of the frequency specific hearing loss. We have re-examined and extended the expression analyses of KCNQ4 in the murine inner ear using RT-PCR and whole mount in situ hybridization. Our results confirmed that the rat KCNQ4 orthologue is expressed in both inner and outer hair cells. Reciprocal longitudinal gradients were found in inner hair cells (IHCs) and OHCs. The strongest expression of KCNQ4 in IHCc was in the base of the cochlea and in the apex for OHCs. Similar to the IHCs, a basal to apical gradient was present in the spiral sensory neurons. IHCs mediate hearing via their afferent sensory neurons, whereas OHCs function as active cochlear amplifiers. The complete absence of OHCs leads only to severe sensitivity reduction, but not complete hearing loss. Our data suggest that the primary defect leading to initial high frequency loss and subsequent progressive hearing loss for all frequencies may be due to spiral ganglion and/or IHC dysfunction, rather than an OHC aberration. (C) 2000 Elsevier Science B.V.
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U2 - 10.1016/S0169-328X(00)00204-7
DO - 10.1016/S0169-328X(00)00204-7
M3 - Article
C2 - 11042367
AN - SCOPUS:0034693298
VL - 82
SP - 137
EP - 149
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1-2
ER -