title: Inducible gene deletion in the entire cardiac conduction system using Hcn4-CreERT2 BAC transgenic mice.
abstract: Developmental defects and disruption of molecular pathways of the cardiac conduction system (CCS) can cause life-threatening cardiac arrhythmias. Despite decades of effort, knowledge about the development and molecular control of the CCS remains primitive. Mouse genetics, complementary to other approaches such as human genetics, has become a key tool for exploring the developmental processes of various organs and associated diseases. Genetic analysis using mouse models will likely provide great insights about the development of the CCS, which can facilitate the development of novel therapeutic strategies to treat arrhythmias. To enable genetic studies of the CCS, CCS-associated Cre mouse models are essential. However, existing mouse models with Cre activity reported in the CCS have various limitations such as Cre leak, haploinsufficiency, and inadequate specificity of the Cre activity. To circumvent those limitations, we successfully generated Hcn4-CreERT2 bacterial artificial chromosome (BAC) transgenic mice using BAC recombineering in which Cre activity was specifically detected in the entire CCS after tamoxifen induction. Our Hcn4-CreERT2 BAC transgenic line will be an invaluable genetic tool with which to dissect the developmental control of CCS and arrhythmias.
authors.affiliation: Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Meng
authors.initials: M
authors.lastname: Wu
authors.forename: Siwu
authors.initials: S
authors.lastname: Peng
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics* / Q000378:metabolism; D004562:Electrocardiography / Q000187:drug effects; D017353:Gene Deletion; D005821:Genetic Techniques; D014644:Genetic Variation; D006329:Heart Conduction System / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000235:genetics*; D019426:Integrases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D011960:Receptors, Estrogen / Q000235:genetics; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: C578706:Hcn4 protein, mouse; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D011960:Receptors, Estrogen; D013629:Tamoxifen; C045073:Cre recombinase; D019426:Integrases
keywords: BAC; Hcn4-CreERT2; cardiac conduction system; inducible Cre line