title: Animal and in silico models for the study of sarcomeric cardiomyopathies.
abstract: Over the past decade, our understanding of cardiomyopathies has improved dramatically, due to improvements in screening and detection of gene defects in the human genome as well as a variety of novel animal models (mouse, zebrafish, and drosophila) and in silico computational models. These novel experimental tools have created a platform that is highly complementary to the naturally occurring cardiomyopathies in cats and dogs that had been available for some time. A fully integrative approach, which incorporates all these modalities, is likely required for significant steps forward in understanding the molecular underpinnings and pathogenesis of cardiomyopathies. Finally, novel technologies, including CRISPR/Cas9, which have already been proved to work in zebrafish, are currently being employed to engineer sarcomeric cardiomyopathy in larger animals, including pigs and non-human primates. In the mouse, the increased speed with which these techniques can be employed to engineer precise 'knock-in' models that previously took years to make via multiple rounds of homologous recombination-based gene targeting promises multiple and precise models of human cardiac disease for future study. Such novel genetically engineered animal models recapitulating human sarcomeric protein defects will help bridging the gap to translate therapeutic targets from small animal and in silico models to the human patient with sarcomeric cardiomyopathy.
authors.affiliation: Division of Experimental Cardiology, Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, The Netherlands d.duncker@erasmusmc.nl l.carrier@uke.de.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Duncker
authors.affiliation: Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Bakkers
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Bianca J
authors.initials: BJ
authors.lastname: Brundel
authors.affiliation: Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital, Cincinnati, OH, USA.
authors.forename: Jeff
authors.initials: J
authors.lastname: Robbins
authors.affiliation: Department of Medicine and Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA.
authors.forename: Jil C
authors.initials: JC
authors.lastname: Tardiff
authors.affiliation: Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Hamburg, Germany d.duncker@erasmusmc.nl l.carrier@uke.de.
authors.forename: Lucie
authors.initials: L
authors.lastname: Carrier
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D002415:Cats; D003198:Computer Simulation; D004285:Dogs; D004330:Drosophila / Q000235:genetics; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D008822:Mice, Transgenic; D023421:Models, Animal; D008955:Models, Cardiovascular; D009154:Mutation; D010641:Phenotype; D012518:Sarcomeres / Q000378:metabolism / Q000473:pathology; D015027:Zebrafish / Q000235:genetics
chemical_list: D005819:Genetic Markers
keywords: Animal models; Cardiomyopathy; Genetics; In silico models; Sarcomeres