TY - JOUR
T1 - Late-onset hearing loss in a mouse model of DFN3 non-syndromic deafness
T2 - Morphologic and immunohistochemical analyses
AU - Xia, An Ping
AU - Kikuchi, Toshihiko
AU - Minowa, Osamu
AU - Katori, Yukio
AU - Oshima, Takeshi
AU - Noda, Tetsuo
AU - Ikeda, Katsuhisa
N1 - Funding Information:
The authors gratefully acknowledge Dr. Nobuo Takagi, University of Hokkaido, for his insightful suggestions for our manuscript. This study was supported by a Grant-in-Aid for Science Research (No. 11557122 to K.I.) from the Ministry of Education, Science and Culture, Japan.
PY - 2002
Y1 - 2002
N2 - Recently, we reported that homozygous males and females of a mouse model of DFN3 non-syndromic deafness generated by the deletion of Brn-4 transcription factor showed profound deafness due to severe alterations in the cochlear spiral ligament fibrocytes from the age of 11 weeks, whereas no hearing loss was recognized in young female heterozygotes. It is known that a part of obligate female carriers of DFN3 showed progressive hearing loss. In the present study, we examined the late-onset effect of Brn-4 deficiency on the hearing organ of the mouse. About one third of heterozygous female mice revealed late-onset profound deafness at the age of 1 year. Furthermore, in these deafened heterozygotes, characteristic abnormalities in Reissner's membrane attachment and type II fibrocytes in the suprastrial zone became evident under light microscope, similar to homozygous female mice. A significant reduction in the immunoreactivity of connexin 26 (Cx26), connexin 31 (Cx31), Na,K-ATPase and Na-K-Cl cotransporter in the spiral ligament fibrocytes was observed in aged heterozygotes showing late-onset profound deafness. The late-onset phenotype observed in heterozygous mutant mice, being consistent with the progressive deafness observed in human female heterozygotes, may be explained by alterations of the ion transport systems in the spiral ligament fibrocytes.
AB - Recently, we reported that homozygous males and females of a mouse model of DFN3 non-syndromic deafness generated by the deletion of Brn-4 transcription factor showed profound deafness due to severe alterations in the cochlear spiral ligament fibrocytes from the age of 11 weeks, whereas no hearing loss was recognized in young female heterozygotes. It is known that a part of obligate female carriers of DFN3 showed progressive hearing loss. In the present study, we examined the late-onset effect of Brn-4 deficiency on the hearing organ of the mouse. About one third of heterozygous female mice revealed late-onset profound deafness at the age of 1 year. Furthermore, in these deafened heterozygotes, characteristic abnormalities in Reissner's membrane attachment and type II fibrocytes in the suprastrial zone became evident under light microscope, similar to homozygous female mice. A significant reduction in the immunoreactivity of connexin 26 (Cx26), connexin 31 (Cx31), Na,K-ATPase and Na-K-Cl cotransporter in the spiral ligament fibrocytes was observed in aged heterozygotes showing late-onset profound deafness. The late-onset phenotype observed in heterozygous mutant mice, being consistent with the progressive deafness observed in human female heterozygotes, may be explained by alterations of the ion transport systems in the spiral ligament fibrocytes.
KW - Brn-4
KW - Cx26
KW - Cx31
KW - Heterozygous female mouse
KW - Na,K-ATPase
KW - Na-K-Cl cotransporter
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U2 - 10.1016/S0378-5955(02)00309-X
DO - 10.1016/S0378-5955(02)00309-X
M3 - Article
C2 - 12062767
AN - SCOPUS:0035985793
VL - 166
SP - 150
EP - 158
JO - Hearing Research
JF - Hearing Research
SN - 0378-5955
IS - 1-2
ER -