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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • December 2000

Published In

Volume / Issue

  • 106 / 12

Start / End Page

  • 1447 - 1455

PubMed ID

  • 11120752

Pubmed Central ID

  • PMC387258

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/JCI10897


  • eng

Conference Location

  • United States