title: Expression of a Mutant kcnj2 Gene Transcript in Zebrafish.
abstract: Long QT 7 syndrome (LQT7, also known as Andersen-Tawil syndrome) is a rare autosomal-dominant disorder that causes cardiac arrhythmias, periodic paralysis, and dysmorphic features. Mutations in the human KCNJ2 gene, which encodes for the subunit of the potassium inwardly-rectifying channel (IK1), have been associated with the disorder. The majority of mutations are considered to be dominant-negative as mutant proteins interact to limit the function of wild type KCNJ2 proteins. Several LQT7 syndrome mouse models have been created that vary in the physiological similarity to the human disease. To complement the LQT7 mouse models, we investigated the usefulness of the zebrafish as an alternative model via a transient approach. Initial bioinformatic analysis identified the zebrafish orthologue of the human KCNJ2 gene, together with a spatial expression profile that was similar to that of human. The expression of a kcnj2-12 transcript carrying an in-frame deletion of critical amino acids identified in human studies resulted in embryos that exhibited defects in muscle development, thereby affecting movement, a decrease in jaw size, pupil-pupil distance, and signs of scoliosis. These defects correspond to some phenotypes expressed by human LQT7 patients.
authors.affiliation: School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Ivone U S
authors.initials: IU
authors.lastname: Leong
authors.affiliation: Greenlane Paediatric and Congenital Cardiac Service, Starship Children's Hospital, Private Bag 92024 Grafton, Auckland 1142, New Zealand.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Skinner
authors.affiliation: Department of Obstetrics and Gynaecology, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Shelling
authors.affiliation: School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand; Diagnostic Genetics, LabPlus, Auckland City Hospital, P.O. Box 110031, Auckland 1142, New Zealand.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Love