Unknown

Dataset Information

0

Targeted disruption of the Kcnq1 gene produces a mouse model of Jervell and Lange-Nielsen Syndrome.

ABSTRACT: KCNQ1 encodes KCNQ1, which belongs to a family of voltage-dependent K(+) ion channel proteins. KCNQ1 associates with a regulatory subunit, KCNE1, to produce the cardiac repolarizing current, I(Ks). Loss-of-function mutations in the human KCNQ1 gene have been linked to Jervell and Lange-Nielsen Syndrome (JLNS), a disorder characterized by profound bilateral deafness and a cardiac phenotype. To generate a mouse model for JLNS, we created a line of transgenic mice that have a targeted disruption in the Kcnq1 gene. Behavioral analysis revealed that the Kcnq1(-/-) mice are deaf and exhibit a shaker/waltzer phenotype. Histological analysis of the inner ear structures of Kcnq1(-/-) mice revealed gross morphological anomalies because of the drastic reduction in the volume of endolymph. ECGs recorded from Kcnq1(-/-) mice demonstrated abnormal T- and P-wave morphologies and prolongation of the QT and JT intervals when measured in vivo, but not in isolated hearts. These changes are indicative of cardiac repolarization defects that appear to be induced by extracardiac signals. Together, these data suggest that Kcnq1(-/-) mice are a potentially valuable animal model of JLNS.

SUBMITTER: Casimiro MC 

PROVIDER: S-EPMC30171 | biostudies-literature | 2001 Feb

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Targeted disruption of the Kcnq1 gene produces a mouse model of Jervell and Lange-Nielsen Syndrome.

Casimiro M C MC   Knollmann B C BC   Ebert S N SN   Vary J C JC   Greene A E AE   Franz M R MR   Grinberg A A   Huang S P SP   Pfeifer K K  

Proceedings of the National Academy of Sciences of the United States of America 20010201 5

KCNQ1 encodes KCNQ1, which belongs to a family of voltage-dependent K(+) ion channel proteins. KCNQ1 associates with a regulatory subunit, KCNE1, to produce the cardiac repolarizing current, I(Ks). Loss-of-function mutations in the human KCNQ1 gene have been linked to Jervell and Lange-Nielsen Syndrome (JLNS), a disorder characterized by profound bilateral deafness and a cardiac phenotype. To generate a mouse model for JLNS, we created a line of transgenic mice that have a targeted disruption in  ...[more]

Similar Datasets

Unknown Jervell and Lange-Nielsen syndrome with novel KCNQ1 and additional gene mutations.
| S-EPMC7562699 | biostudies-literature
Unknown Novel frameshift mutation in the KCNQ1 gene responsible for Jervell and Lange-Nielsen syndrome.
| S-EPMC5776430 | biostudies-literature
Unknown Large deletion in KCNQ1 identified in a family with Jervell and Lange-Nielsen syndrome.
| S-EPMC4151011 | biostudies-literature
Unknown A cryptic splice-altering KCNQ1 variant in trans with R259L leading to Jervell and Lange-Nielsen syndrome.
| S-EPMC7933243 | biostudies-literature
Unknown Virally mediated Kcnq1 gene replacement therapy in the immature scala media restores hearing in a mouse model of human Jervell and Lange-Nielsen deafness syndrome.
| S-EPMC4551345 | biostudies-literature
Unknown Detection of a new KCNQ1 frameshift mutation associated with Jervell and Lange-Nielsen syndrome in 2 Iranian families.
| S-EPMC6010008 | biostudies-literature
Unknown Jervell and Lange-Nielsen Syndrome due to a Novel Compound Heterozygous <i>KCNQ1</i> Mutation in a Chinese Family.
| S-EPMC7246397 | biostudies-literature
Unknown Partial Duplication and Poly(A) Insertion in KCNQ1 Not Detected by Next-Generation Sequencing in Jervell and Lange-Nielsen Syndrome.
| S-EPMC4905601 | biostudies-literature
Unknown Genotype-phenotype analysis of three Chinese families with Jervell and Lange-Nielsen syndrome.
| S-EPMC3354473 | biostudies-literature
Unknown Gene therapy via canalostomy approach preserves auditory and vestibular functions in a mouse model of Jervell and Lange-Nielsen syndrome type 2.
| S-EPMC7846845 | biostudies-literature