ArticleCirculation2005
Transgenic mouse model of ventricular preexcitation and atrioventricular reentrant tachycardia induced by an AMP-activated protein kinase loss-of-function mutation responsible for Wolff-Parkinson-White syndrome.
Article in Circulation, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 144 citations in OpenAlex.
- Arrhythmias in patients receiving enzyme replacement therapy for infantile Pompe disease.Genetics in medicine : official journal of the American College of Medical Genetics · 2008Trial
- A New Mechanism of Supraventricular Tachycardia: Gene Mutation.Current cardiology reviews · 2025Review
- The metabolic sensor AMPK: Twelve enzymes in one.Molecular metabolism · 2024Review
- When Paying Attention Pays Back: Missense Mutation c.1006G>A p. (Val336Ile) inInternational journal of molecular sciences · 2024Review
- New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models.Scientific reports · 2023Article
- Toll-Like Receptor 4 (TLR4) and AMPK Relevance in Cardiovascular Disease.Advanced pharmaceutical bulletin · 2023Review
- Kennedy's disease presented with mastication fatigue combined with positive titin antibody: a case report.BMC neurology · 2022Article
- Controversial molecular functions of CBS versus non-CBS domain variants of PRKAG2 in arrhythmia and cardiomyopathy: A case report and literature review.Molecular genetics & genomic medicine · 2022Review
- Structure-function analysis of the AMPK activator SC4 and identification of a potent pan AMPK activator.The Biochemical journal · 2022Article
- Animal Models to Study Cardiac Arrhythmias.Circulation research · 2022Review
- Atrial Lesions in a Pedigree WithFrontiers in cardiovascular medicine · 2022Article
- Genetic Risk Stratification: A Paradigm Shift in Prevention of Coronary Artery Disease.JACC. Basic to translational science · 2021Review
- A Journey through Genetic Architecture and Predisposition of Coronary Artery Disease.Current genomics · 2020Review
- Familial Atrial Enlargement, Conduction Disorder and Symmetric Cardiac Hypertrophy Are Early Signs of PRKAG2 R302Q.Current medical science · 2020Article
- Identification, clinical manifestation and structural mechanisms of mutations in AMPK associated cardiac glycogen storage disease.EBioMedicine · 2020Article
- West Nile virus capsid protein inhibits autophagy by AMP-activated protein kinase degradation in neurological disease development.PLoS pathogens · 2020Article
- A novel PRKAG2 mutation in a Chinese family with cardiac hypertrophy and ventricular pre-excitation.Scientific reports · 2017Article
- Targeting the energy guardian AMPK: another avenue for treating cardiomyopathy?Cellular and molecular life sciences : CMLS · 2017Review
- Integrative Analysis of PRKAG2 Cardiomyopathy iPS and Microtissue Models Identifies AMPK as a Regulator of Metabolism, Survival, and Fibrosis.Cell reports · 2016Article
- Genome editing with CRISPR/Cas9 in postnatal mice corrects PRKAG2 cardiac syndrome.Cell research · 2016Article
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
backgroundWe identified a gene (PRKAG2) that encodes the gamma-2 regulatory subunit of AMP-activated protein kinase (AMPK) with a mutation (Arg302Gln) responsible for familial Wolff-Parkinson-White (WPW) syndrome. The human phenotype consists of ventricular preexcitation, conduction abnormalities, and cardiac hypertrophy. METHODS AND
resultsTo elucidate the molecular basis for the phenotype, transgenic mice were generated by cardiac-restricted expression of the wild-type (TG(WT)) and mutant(TG(R302Q)) PRKAG2 gene with the cardiac-specific promoter alpha-myosin heavy chain. ECG recordings and intracardiac electrophysiology studies demonstrated the TG(R302Q) mice to have ventricular preexcitation (PR interval 10+/-2 versus 33+/-5 ms in TG(WT), P<0.05) and a prolonged QRS (20+/-5 versus 10+/-1 ms in TG(WT), P<0.05). A distinct AV accessory pathway was confirmed by electrical and pharmacological stimulation and substantiated by induction of orthodromic AV reentrant tachycardia. Enzymatic activity of AMPK in the mutant heart was significantly reduced (0.009+/-0.003 versus 0.025+/-0.001 nmol x min(-1) x g(-1) in nontransgenic mice), presumably owing to the mutation disrupting the AMP binding site. Excessive cardiac glycogen was observed. Hypertrophy was confirmed by increases in heart weight (296 versus 140 mg in TG(WT)) and ventricular wall thickness.
conclusionsWe have developed a genetic animal model of WPW that expresses a mutation responsible for a familial form of WPW syndrome with a phenotype identical to that of the human, including induction of supraventricular arrhythmia. The defect is due to loss of function of AMPK. Elucidation of the molecular basis should provide insight into development of the cardiac conduction system and accessory pathways.
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