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半拷贝基因NKCC1杂合小鼠与年龄相关性听力下降的关系 被引量:3

Association of age-related hearing loss with mice which expressed only one copy of gene encoding NKCC1 co-transporter
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摘要 目的培育杂合子NKCCl+/-和野生型NKCCl+/+小鼠,观察携带不同拷贝基因的NKCCl小鼠的年龄相关性听力表现,研究NKCCl基因及其离子通道在年龄相关性听力下降(age- related hearing loss,AHL)中的作用,并初步探讨其可能发生的机制。方法运用NKCCl+/-杂合子小鼠和NKCCl+/+野生型小鼠为平台,于小鼠生长过程中的各个年龄段分别检测小鼠的听性脑干反应(auditory brainstem response,ABR)和耳蜗内电位(endocochlear potential,EP);同时采用扫描电镜进行耳蜗形态学观察和免疫印迹杂交检测不同鼠龄小鼠耳蜗的NKCCl通道蛋白的含量。结果NKCCl+/-杂合子小鼠与NKCCl+/+野生型小鼠相比较,其ABR检测短声阈值在每一年龄组的各测试频率均升高,各年龄组相比较差异有统计学意义(P值均<0.05)。NKCCl+/-杂合子半拷贝基因鼠的听力随年龄增长而逐渐下降,与低龄鼠相比,老龄鼠的ABR阈值显著性升高(P值均< 0.05)。NKCCl+/-小鼠的EP也随年龄增长而呈下降趋势,老龄小鼠的EP值与其低龄鼠相比明显降低(P<0.05)。老龄小鼠的耳蜗NKCCl蛋白含量低于低龄鼠。与老龄NKCCl+/+鼠相比较,老龄NKCCI+/-鼠的耳蜗底回外毛细胞出现散在的点状缺失。结论当NKCCl基因呈现半拷贝复制时小鼠可呈现AHL,NKCCl基因可能在AHL的发病中起一定的作用。AHL的发病可能与NKCCl通道蛋白的遗传特性及功能有关,还可能与NKCCl+/-鼠出现的耳蜗底回外毛细胞缺失有关。 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 NKCCI gene( NKCCI +/- ) 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.
出处 《中华耳鼻咽喉头颈外科杂志》 CAS CSCD 北大核心 2006年第7期537-541,共5页 Chinese Journal of Otorhinolaryngology Head and Neck Surgery
基金 国家自然科学基金资助项目(30371526) 湖北省自然科学基金资助项目(2002AB127) 教育部留学回国人员启动基金资助项目(教外司留2004-527)
关键词 基因 离子通道 年龄因素 膜蛋白质类 Genes Ion channels Deaf Age factors Membrane proteins
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参考文献16

  • 1Johnson KR, Erway LC, Cook SA, et al. A major gene affecting age-related hearing loss in C57BL/6J mice. Hear Res ,1997 ,114 :83-92.
  • 2Spicer SS, Schulte BA. Evidence for a medial K^+ recycling pathway from inner hair cells. Hear Res, 1998,118 : 1-12.
  • 3Zheng QY, Johnson KR. Hearing loss associated with the modifier of deaf waddler (mdfw) locus corresponds with age-related hearing loss in 12 inbred strains of mice. Hear Res,2001,154:45-53.
  • 4Sakaguchi N, Crouch JJ, Lytle C. Na-K-Cl co-transport expression in the developing and senescent gerbil cochlea. Hear Res, 1998,118 :114-122.
  • 5Crouch JJ, Sakaguchi N, Lytle C, et al.Immunohistochemical localization of the Na-K-Cl Co-transporter ( NKCC1 ) in the gerbil inner ear. J Histochem Cytochem,1997, 45:773-778.
  • 6Delpire E, Lu J, England R, et al. Deafness and imbalance associated with inactivation of the secretory Na-K-2Cl co-transporter. Nat genet,1999,22:192-195.
  • 7Weber PC, Cunningham CD 3rd, Schulte BA. Potassium recycling pathways in the human cochlea. Laryngoscope, 2001, 111 : 1156-1165.
  • 8Erichsen S, Zuo J, Curtis L, et al. Na,K-ATPase alpha- and beta-isoforms in the developing cochlea of the mouse. Hear Res, 1996,100 : 143-149.
  • 9Wangemann P. K^+ cycling and the endocochlear potiential. Hear Res,2002,165:1-9.
  • 10Xia A, Kikuchi T, Hozawa K, et al. Expression of connexin 26 and Na, K-ATPase in the developing mouse cochlear lateral wall:functional implications. Brain Res, 1999, 846 : 106-111.

同被引文献26

  • 1褚汉启,熊浩,周小琴,黄孝文,周良强,崔永华.Localization of NKCC1 in the Cochlea and Morphology of the Cochlea in NKCC1-Knockout Mice[J].Journal of Huazhong University of Science and Technology(Medical Sciences),2006,26(3):374-377. 被引量:3
  • 2褚汉启,黄孝文,熊浩,韩芳,吴振恭,周良强,崔永华.小鼠耳蜗侧壁α_2 Na,K-ATPase在听觉及年龄相关性听力下降中的作用[J].听力学及言语疾病杂志,2006,14(6):429-432. 被引量:2
  • 3褚汉启,黄孝文,周良强,熊浩,韩芳,吴振恭,王春芳,张平,崔永华.KCNQ1基因缺失致小鼠听觉丧失和耳蜗形态异常[J].中华耳鼻咽喉头颈外科杂志,2006,41(11):867-868. 被引量:2
  • 4Davis H.Biophysics and physiology of the inner ear[J].Physiol Rev,1957,37(1):1-49.
  • 5Weber PC,Cunningham CD,Schulte BA.Potassium recycling pathways in the human cochlea[J].Laryngoscope,2001,111(7):1156-1165.
  • 6Wangemann P.K+ cycling and the endocochlear potential[J].Hear Res,2002,165(1-2):1-9.
  • 7Crouch JJ,Sakaguchi N,Lytle C,et al.Immunohistochemical localization of the Na-K-Cl co-transporter (NKCC1) in the gerbil inner ear[J].J Histochem Cytochem,1997,45(6):773-778.
  • 8Schulte BA,Steel KP.Expression of alpha and beta subunit isoforms of Na,K-ATPase in the mouse inner ea r and changes with mutations at the Wv or Sld loci[J].Hear Res,1994,78(1):65-76.
  • 9Forge A,Wright A,Davies S.Analysis of structural changes in the stria vascularis following chronic gentamicin treatment[J].Hear Res,1987,31(3):253-266.
  • 10Taylor RR,Nevill G,Forge A.Rapid hair cell loss:a mouse model for auditory lesions[J].J Assoc Res Otolaryngol,2008,9(1):44-64.

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