WTC deafness Kyoto (dfk):: a rat model for extensive investigations of Kcnq1 functions
WTC deafness Kyoto (dfk):: a rat model for extensive investigations of Kcnq1 functions
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DOI：
10.1152/physiolgenomics.00221.2005
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发表时间：
2006-02-23
影响因子：
4.6
通讯作者：
Serikawa, T
中科院分区：
文献类型：
--
作者：
Gohma, H;Kuramoto, T;Serikawa, T
KCNQ 1通过与调节亚基KCNE蛋白组装形成K+通道，并在多种组织中的K+稳态中起关键作用。在心脏中，KCNQ 1与KCNE 1共同组装产生心脏延迟整流钾电流。在内耳中，KCNQ 1/KCNE 1复合物维持内淋巴中高浓度的K+。在胃中，KCNQ 1与KCNE 2共同组装形成胃酸分泌所必需的K+外流通道。在结肠和小肠中，KCNQ 1与KCNE 3共组装，在跨上皮cAMP刺激的Cl-分泌中发挥重要作用。为了进一步了解Kcnq 1在体内的功能，需要动物模型。在这里，我们报告了一个coisogenic Kcnq 1突变大鼠，命名为耳聋京都（dfk），其表型的特点。WTC-dfk大鼠携带Kcnq 1基因内缺失，表现出体重增加受损、耳聋和内淋巴显著减少导致的不平衡、心电图（ECG）QT间期延长以及与胃粘膜肥大相关的胃无氯血症。令人惊讶的是，WTC-dfk大鼠表现出高血压，这表明Kcnq 1可能参与了血压的调节。这些研究结果表明，WTC-dfk大鼠可能是研究KCNQ 1生理功能和建立KCNQ 1相关疾病新治疗方法的有力工具。
KCNQ1 forms K+ channels by assembly with regulatory subunit KCNE proteins and plays a key role in the K+ homeostasis in a variety of tissues. In the heart, KCNQ1 is coassembled with KCNE1 to produce a cardiac delayed rectifier K+ current. In the inner ear, the KCNQ1/ KCNE1 complex maintains the high concentration of K+ in the endolymph. In the stomach, KCNQ1 is coassembled with KCNE2 to form the K+ exflux channel that is essential for gastric acid secretion. In the colon and small intestine, KCNQ1 is coassembled with KCNE3 to play an important role in transepithelial cAMP-stimulated Cl- secretion. For further understanding of Kcnq1 function in vivo, an animal model has been required. Here we reported the identification of a coisogenic Kcnq1 mutant rat, named deafness Kyoto (dfk), and the characterization of its phenotypes. WTC-dfk rats carried intragenic deletion at the Kcnq1 gene and showed impaired gain of weight, deafness, and imbalance resulting from the marked reduction of endolymph, prolonged QT interval in the electrocardiogram ( ECG), and gastric achlorhydria associated with hypertrophic gastric mucosa. Surprisingly, WTC-dfk rats showed hypertension, which suggested that Kcnq1 might be involved in the regulation of blood pressure. These findings suggest that WTC-dfk rats could represent a powerful tool for studying the physiological functions of KCNQ1 and for the establishment of new therapeutic procedures for Kcnq1-related diseases.