title: WTC deafness Kyoto (dfk): a rat model for extensive investigations of Kcnq1 functions.
abstract: 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.
authors.affiliation: Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Gohma
authors.forename: Takashi
authors.initials: T
authors.lastname: Kuramoto
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kuwamura
authors.forename: Ryoko
authors.initials: R
authors.lastname: Okajima
authors.forename: Noriaki
authors.initials: N
authors.lastname: Tanimoto
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Yamasaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nakanishi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kitada
authors.forename: Takeru
authors.initials: T
authors.lastname: Makiyama
authors.forename: Masaharu
authors.initials: M
authors.lastname: Akao
authors.forename: Toru
authors.initials: T
authors.lastname: Kita
authors.forename: Masashi
authors.initials: M
authors.lastname: Sasa
authors.forename: Tadao
authors.initials: T
authors.lastname: Serikawa
mesh_terms: D000483:Alleles; D000818:Animals; D001835:Body Weight; D003638:Deafness / Q000503:physiopathology; D007758:Ear, Inner / Q000002:abnormalities; D004562:Electrocardiography; D005091:Exons; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D017353:Gene Deletion; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000378:metabolism; D051657:KCNQ1 Potassium Channel / Q000235:genetics* / Q000502:physiology*; D023421:Models, Animal; D008957:Models, Genetic; D009154:Mutation; D010641:Phenotype; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D051657:KCNQ1 Potassium Channel