Animal and in silico models for the study of sarcomeric cardiomyopathies

TY - JOUR

T1 - Animal and in silico models for the study of sarcomeric cardiomyopathies

AU - Duncker, Dirk J

AU - Bakkers, Jeroen

AU - Brundel, Bianca J

AU - Robbins, Jeff

AU - Tardiff, Jil C

AU - Carrier, Lucie

N1 - Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

PY - 2015/4/1

Y1 - 2015/4/1

N2 - 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.

AB - 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.

U2 - 10.1093/cvr/cvv006

DO - 10.1093/cvr/cvv006

M3 - SCORING: Journal article

C2 - 25600962

VL - 105

SP - 439

EP - 448

JO - CARDIOVASC RES

JF - CARDIOVASC RES

SN - 0008-6363

IS - 4

ER -