Replacement by homologous recombination of the minK gene with lacZ reveals restriction of minK expression to the mouse cardiac conduction system.

  title={Replacement by homologous recombination of the minK gene with lacZ reveals restriction of minK expression to the mouse cardiac conduction system.},
  author={Sabina Kupershmidt and T. Yang and M. E. Anderson and Andy Wessels and Kevin D. Niswender and Mark A. Magnuson and Dan M. Roden},
  journal={Circulation research},
  volume={84 2},
The minK gene encodes a 129-amino acid peptide the expression of which modulates function of cardiac delayed rectifier currents (IKr and IKs), and mutations in minK are now recognized as one cause of the congenital long-QT syndrome. We have generated minK-deficient mice in which the bacterial lacZ gene has been substituted for the minK coding region such that beta-galactosidase expression is controlled by endogenous minK regulatory elements. In cardiac myocytes isolated from wild-type neonatal… 

Figures from this paper

Inhibition of cardiac delayed rectifier K+ currents by an antisense oligodeoxynucleotide against IsK (minK) and over-expression of IsK mutant D77N in neonatal mouse hearts

Results indicate that the IsK protein associates with both KvLQT1 and ERG products to modulate IKr and IKs in cardiac myocytes.

Recombinase‐mediated cassette exchange to rapidly and efficiently generate mice with human cardiac sodium channels

Data demonstrate that RMCE can be used to generate mice in which a targeted allele can be rapidly and efficiently replaced by variants of choice, and thereby can serve as an enabling approach for the functional characterization of ion channel and other DNA variants.

Inducible recombination in the cardiac conduction system of minK: CreERT2 BAC transgenic mice

To enable inducible recombination in the murine CCS, a minK:CreERT2 bacterial artificial chromosome (BAC) transgenic mouse line is created that is present after tamoxifen administration in the atrioventricular (AV) node, AV bundle, and bundle branches of adult transgenic mice.

Targeted Replacement of Kv1.5 in the Mouse Leads to Loss of the 4-Aminopyridine-Sensitive Component of IK,slow and Resistance to Drug-Induced QT Prolongation

Kv1.5 encodes the 4-AP-sensitive component of IK,slow in the mouse ventricle and confers sensitivity to 4- AP-induced prolongation of APD and QTc and may explain the phenotypic differences between SWAP mice and the previously described transgenic mice expressing a truncated dominant-negative Kv2.1 construct.

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

Data suggest that Kcnq1−/− mice are a potentially valuable animal model of JLNS, a disorder characterized by profound bilateral deafness and a cardiac phenotype caused by loss-of-function mutations in the human KCNQ1 gene.

Summary The T-Box transcription factor Tbx 5 is required for the patterning and maturation of the murine cardiac conduction system

A critical role is reported for the T-box transcription factor Tbx5 in development and maturation of the cardiac conduction system, and it is suggested that the electrophysiologic defects in Holt–Oram syndrome reflect a developmental abnormality of theconduction system.

Morphogenesis of the right ventricle requires myocardial expression of Gata4.

A general role of myocardial Gata4 in regulating cardiomyocyte proliferation and a specific, stage-dependent role in regulating the morphogenesis of the RV and the atrioventricular canal are demonstrated.



Coassembly of KVLQT1 and minK (IsK) proteins to form cardiac IKS potassium channel

KVLQT1 is the subunit that coassembles with minK to form IKS channels and IKS dysfunction is a cause of cardiac arrhythmia, and is shown to encode a K+ channel with biophysical properties unlike other known cardiac currents.

Anti-minK antisense decreases the amplitude of the rapidly activating cardiac delayed rectifier K+ current.

The rapidly and slowly activating delayed rectifier K+ currents (IKr and IKs, respectively), which have different physiological properties have been identified in cardiac cells from several species, including humans, and the role of this gene product in channel function remains controversial.

KvLQT1 and IsK (minK) proteins associate to form the IKS cardiac potassium current

It is shown that KVLQT1 associates with IsK to form the channel underlying the IKS cardiac current, which is a target of class-Ill anti-arrhythmic drugs and is involved in the L QT1 syndrome.

Two isoforms of the mouse ether-a-go-go-related gene coassemble to form channels with properties similar to the rapidly activating component of the cardiac delayed rectifier K+ current.

A novel N-terminal Erg isoform is identified that is expressed specifically in the heart, has rapid deactivation kinetics, and coassembles with the longer isoform in Xenopus oocytes.

Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel.

K(V)LQT1 is the subunit that coassembles with minK to form I(Ks) channels and I( Ks) dysfunction is a cause of cardiac arrhythmia.

Expression of a minimal K+ channel protein in mammalian cells and immunolocalization in guinea pig heart.

The first expression of minK activity in transiently transfected mammalian (HEK 293) cells is reported and it is demonstrated that the characteristics of the expressed minK current are similar to those of IKs recorded from guinea pig heart cells under similar experimental conditions, providing strong evidence that a minK-like protein underlies Iks.

A minK–HERG complex regulates the cardiac potassium current IKr

It is shown that HERG and minK form a stable complex, and that this heteromultimerization regulates IKr activity, which is central to the control of the heart rate and rhythm.

Involvement of IsK-associated K+ channel in heart rate control of repolarization in a murine engineered model of Jervell and Lange-Nielsen syndrome.

It is concluded that the isk gene product and/or ISKs, when present, blunts the QT adaptation to heart rate variations and that steeper QT-RR relationships reflect a greater susceptibility to arrhythmias in patients lacking IKs.

Electrophysiological characterization of an alternatively processed ERG K+ channel in mouse and human hearts.

ERG B, an alternatively processed isoform of the ERG gene, expressed selectively in heart and with electrophysiological characteristics similar to those of native cardiac IKr is identified.

Cloning, expression, pharmacology and regulation of a delayed rectifier K+ channel in mouse heart.

Cultured newborn mouse ventricular cardiac cells exhibited a delayed rectifier K+ current which had biophysical properties similar to those of cloned mIsK and which was inhibited by clofilium and protein kinase C activators.