title: [Association of age-related hearing loss with ion transporter KCNQ1 and NKCC1 in cochlea of C57BL/6J mice].
abstract: OBJECTIVE
  To investigate the age-related expression of KCNQ1 and NKCC1 ion transporters in the stria vascularis in the cochlea of C57BL/6J mice, and to analyze the relationship between the two ion transporters and age-related hearing loss.
  
  
  METHODS
  Auditory function of C57BL/6J mice was measured by auditory brainstem response (ABR) at the ages of 4, 8, 14, 24, 40 weeks old respectively. The location of KCNQ1 and NKCC1 ion transporters in the cochlea of C57BL/6J mice was detected by immunohistochemistry staining. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the levels of KCNQ1 and NKCC1 mRNA in the cochlea of C57BL/6J mice at different ages.
  
  
  RESULTS
  The mean values for ABR thresholds in response to click, 4 kHz and 8 kHz sound stimulus of C57BL/6J mice gradually increased with age. The ABR thresholds of the mice of over 14 weeks age were significantly elevated in comparison with lower ages (P < 0.05). In the lateral wall of C57BL/6J mice cochlea, the KCNQ1 protein was mainly expressed at the apical membrane of the strial marginal cells. The localization of NKCC1 protein was mainly present at the basolateral membrane of the stria marginal cells, spiral ligament and the fibrocytes in the inferior portion of spiral limbus. Expression of KCNQ1 and NKCC1 protein in cochlea of C57BL/6J mice showed age-related decreasing. The level of KCNQ1 and NKCC1 mRNA in cochlea of C57BL/6J also showed a age-related decreasing trend. There was a significant reducing of KCNQ1 mRNA level between C57BL/6J mice of 40 and 4 weeks old (P < 0.05). In comparison with the C57BL/6J mice of 4 weeks old, the NKCC1 mRNA levels of 24 and 40 weeks old also showed significant reducing (P < 0.05).
  
  
  CONCLUSIONS
  The mean value for ABR thresholds of C57BL/6J mice gradually increased with age. Expression of KCNQ1 and NKCC1 protein in the stria vascularis of C57BL/6J mice decreases with age. The levels of KCNQ1 and NKCC1 mRNA in cochlea of C57BL/6J showed a age-related reducing trend. Regulating after post-translation may also participate in the adjusting of the age-related decreasing of KCNQ1 and NKCC1 protein in the cochlea of C57BL/6J mice. KCNQ1 and NKCC1 ion transporters may play a critical role in maintaining normal hearing function of inner ear.
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Jian-Ling
authors.initials: JL
authors.lastname: Li
authors.forename: Han-Qi
authors.initials: HQ
authors.lastname: Chu
authors.forename: Liang-Qiang
authors.initials: LQ
authors.lastname: Zhou
authors.forename: Hao
authors.initials: H
authors.lastname: Xiong
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Qing-Guo
authors.initials: QG
authors.lastname: Chen
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Li
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: Yong-Hua
authors.initials: YH
authors.lastname: Cui
mesh_terms: D000367:Age Factors; D000818:Animals; D003051:Cochlea / Q000378:metabolism* / Q000502:physiology*; D016057:Evoked Potentials, Auditory, Brain Stem; D051657:KCNQ1 Potassium Channel / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism*; D064506:Solute Carrier Family 12, Member 2
chemical_list: D051657:KCNQ1 Potassium Channel; C496910:Kcnq1 protein, mouse; C578878:Slc12a2 protein, mouse; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2