• heart conduction disease

This report describes a fly model of cardiac arrhythmia using alleles of the fly gene KCNQ, which encodes a voltage-gated potassium channel. Dmel\KCNQ is orthologous to the five members of the 'subfamily Q' potassium voltage-gated channel genes in human, KCNQ1, KCNQ2, KCNQ3, KCNQ4, KCNQ5. The human genes are implicated in multiple diseases; KCNQ1 is implicated in several forms of cardiac arrhythmia, most of which exhibit autosomal dominant inheritance (long QT syndrome 1, MIM:192500, FBhh0000304; short QT syndrome 2, MIM:609621; familial atrial fibrillation 3, MIM:607554); Jervell and Lange-Nielsen syndrome (MIM:220400) exhibits autosomal recessive inheritance. For the Dmel\KCNQ gene, classical amorphic alleles, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated.

One of the related human genes, Hsap\KCNQ2, has been introduced into flies, but has not been characterized.

Homozygous loss-of-function mutations of Dmel\KCNQ result in female sterility; eggs laid by homozygous females fail to hatch (maternal effect lethal) and are arrested at a very early stage of development. Homozygous animals from heterozygous mothers survive to adulthood; they show increased incidence of pacing-induced cardiac dysfunction compared to age-matched controls; these phenotypes increase in severity with age. Physical interactions of Dmel\KCNQ have been described; see below and in the KCNQ gene report.

[updated Feb. 2018 by FlyBase; FBrf0222196]