WTC deafness Kyoto (dfk): a rat model for extensive investigations ofKcnq1functions
| Autor: | Takashi Kuramoto, Masaharu Akao, Noriaki Tanimoto, S Nakanishi, Masashi Sasa, Toru Kita, Mitsuru Kuwamura, Hiroshi Gohma, Takeru Makiyama, Kazuhiro Kitada, Tadao Serikawa, Ken-ichi Yamasaki, Ryoko Okajima |
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| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_specialty
endocrine system diseases Physiology Protein subunit Rat model Deafness Biology Body weight Gastric Acid Electrocardiography Internal medicine Genetics medicine Animals Alleles Models Genetic urogenital system Body Weight Rats Inbred Strains Exons Hydrogen-Ion Concentration Gene deletion Rats Cell biology Phenotype Endocrinology Gastric Mucosa Ear Inner Hypertension KCNQ1 Potassium Channel Models Animal Mutation Gene Deletion Homeostasis |
| Zdroj: | Physiological Genomics. 24:198-206 |
| ISSN: | 1531-2267 1094-8341 |
| DOI: | 10.1152/physiolgenomics.00221.2005 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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