Targeted disruption of the Kvlqt1 gene causes deafness and gastric hyperplasia in mice.

Lee MP, Ravenel JD, Hu RJ, Lustig LR, Tomaselli G, Berger RD, Brandenburg SA, Litzi TJ, Bunton TE, Limb C, Francis H, Gorelikow M, Gu H, Washington K, Argani P, Goldenring JR, Coffey RJ, Feinberg AP
J Clin Invest. 2000 106 (12): 1447-55

PMID: 11120752 · PMCID: PMC387258 · DOI:10.1172/JCI10897

The KvLQT1 gene encodes a voltage-gated potassium channel. Mutations in KvLQT1 underlie the dominantly transmitted Ward-Romano long QT syndrome, which causes cardiac arrhythmia, and the recessively transmitted Jervell and Lange-Nielsen syndrome, which causes both cardiac arrhythmia and congenital deafness. KvLQT1 is also disrupted by balanced germline chromosomal rearrangements in patients with Beckwith-Wiedemann syndrome (BWS), which causes prenatal overgrowth and cancer. Because of the diverse human disorders and organ systems affected by this gene, we developed an animal model by inactivating the murine Kvlqt1. No electrocardiographic abnormalities were observed. However, homozygous mice exhibited complete deafness, as well as circular movement and repetitive falling, suggesting imbalance. Histochemical study revealed severe anatomic disruption of the cochlear and vestibular end organs, suggesting that Kvlqt1 is essential for normal development of the inner ear. Surprisingly, homozygous mice also displayed threefold enlargement by weight of the stomach resulting from mucous neck cell hyperplasia. Finally, there were no features of BWS, suggesting that Kvlqt1 is not responsible for BWS.

MeSH Terms (25)

Animals Brain Stem Cochlea Deafness Disease Models, Animal Ear, Inner Electrocardiography Evoked Potentials, Auditory, Brain Stem Female Histocytochemistry Humans Hyperplasia KCNQ1 Potassium Channel KCNQ Potassium Channels Locomotion Long QT Syndrome Male Mice Mice, Knockout Mutation Organ Size Phenotype Potassium Channels Potassium Channels, Voltage-Gated Stomach

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