Inner ear abnormalities in a Kcnq1 (Kvlqt1) knockout mouse: a model of Jervell and Lange-Nielsen syndrome.

Journal Article (Journal Article)

HYPOTHESIS: Mice lacking functional KCNQ1 (previously known as KvLQT1) channels exhibit functional and structural abnormalities that indicate disturbed production of endolymph. BACKGROUND: Congenital deafness associated with cardiac conduction abnormalities (Jervell and Lange-Nielsen syndrome) is associated with dysfunctional KCNQ1/KCNE1 channel complex. This potassium channel plays a critical role in the production and homeostasis of endolymph by the stria vascularis. A preliminary report documented severe abnormalities of the scala media and vestibular compartments of a single mouse lacking functional KCNQ1 alleles. METHODS: Hearing thresholds were measured in three Kcnq1 knockout mice, two heterozygous mice, and one wild-type mouse by auditory brainstem response recordings using clicks, after which the temporal bones were removed. After fixation and dehydration, the ears were embedded in araldite, sectioned at 20-microm thickness, stained with toluidine blue on glass slides, and examined with the light microscope. RESULTS: Kcnq1 knockout mice were deaf and demonstrated circling behavior. They exhibited a marked atrophy of the stria vascularis, contraction of the endolymphatic compartments, and collapse and adhesion of surrounding membranes. There was a complete degeneration of the organ of Corti and an associated degeneration of the spiral ganglion. CONCLUSION: Kcnq1 knockout mice exhibit histopathologic findings that are comparable to those reported in human temporal bone cases of Jervell and Lange-Nielsen syndrome, and provide further evidence that KCNQ1 channel dysfunction can lead to congenital deafness in this syndrome.

Full Text

Duke Authors

Cited Authors

  • Rivas, A; Francis, HW

Published Date

  • May 2005

Published In

Volume / Issue

  • 26 / 3

Start / End Page

  • 415 - 424

PubMed ID

  • 15891643

International Standard Serial Number (ISSN)

  • 1531-7129

Digital Object Identifier (DOI)

  • 10.1097/01.mao.0000169764.00798.84


  • eng

Conference Location

  • United States