[Association of age-related hearing loss with mice which expressed only one copy of gene encoding NKCC1 co-transporter].
OBJECTIVE
To generate transgenic mice of NKCC1 +/- (heterozygous) and NKCC1 +/+ (wild-type) that have a targeted disruption in the NKCC1 gene in order to investigate the relationship of one copy of NKCC1 gene (NKCC1 +/-) and age-related hearing loss (AHL) and to study the possible pathogenesis of AHL METHODS: Auditory function of NKCC1 +/- mice was detected regularly by auditory brain response (ABR) and endocochlear potential (EP). Morphology of cochlea was observed by scanning electron microscope and content of NKCC1 protein was detected by Western blot.


RESULTS
The mean value for ABR thresholds was elevated in NKCC1 +/- mice more than that of NKCC1 +/+ mice (P < 0.01). A progression of age-related hearing loss was found in NKCC1 +/- mice. Compared with younger NKCC1 +/- mice, the mean value for ABR thresholds in aged NKCC1 +/- mice was significantly increased (P < 0.05). The EP of NKCC1 +/- aged mice was also significantly decreased more than that of the younger NKCC1 +/+ mice (P < 0.05). And content of NKCC1 protein were reduced with the growth of the age. The scanning electron microscope showed a kind of scattered punctiform absence of outer hair cells in elder NKCC1 +/- mice cochlea.


CONCLUSIONS
NKCC1 gene maybe takes part in the pathogenesis of AHL. Mice that expressed only one copy of NKCC1 could lead to AHL. AHL may be correlative with the amounts of NKCC1 protein and its function and also with the loss of outer hair cells perhaps.
Chu
Han-Qi
HQ
Department of Otorhinolaryngology, Tongji Hospital, Tongji Medical College, Hua-zhong University of Science and Technology, Wuhan 430030, China. qi7chu@163.com
Xiong
Hao
H
Han
Fang
F
Wu
Zhen-Gong
ZG
Huang
Xiao-Wen
XW
Cui
Yong-Hua
YH
D000367:Age Factors; D000375:Aging / Q000235:genetics* / Q000502:physiology; D000818:Animals; D006311:Hearing Disorders / Q000209:etiology* / Q000235:genetics*; D006579:Heterozygote; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics*; D064506:Solute Carrier Family 12, Member 2
C578878:Slc12a2 protein, mouse; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2