Transgenic rabbit models for cardiac disease research

To study the pathophysiology of human cardiac diseases and to develop novel treatment strategies, complex interactions of cardiac cells on cellular, tissue and on level of the whole heart need to be considered. As in vitro cell-based models do not depict the complexity of the human heart, animal models are used to obtain insights that can be translated to human diseases. Mice are the most commonly used animals in cardiac research. However, differences in electrophysiological and mechanical cardiac function and a different composition of electrical and contractile proteins limit the transferability of the knowledge gained. Moreover, the small heart size and fast heart rate are major disadvantages. In contrast to rodents, electrophysiological, mechanical and structural cardiac characteristics of rabbits resemble the human heart more closely, making them particularly suitable as an animal model for cardiac disease research. In this review, various methodological approaches for the generation of transgenic rabbits for cardiac disease research, such as pronuclear microinjection, the sleeping beauty transposon system and novel genome-editing methods (ZFN and CRISPR/Cas9)will be discussed. In the second section, we will introduce the different currently available transgenic rabbit models for monogenic cardiac diseases (such as long QT syndrome, short-QT syndrome and hypertrophic cardiomyopathy) in detail, especially in regard to their utility to increase the understanding of pathophysiological disease mechanisms and novel treatment options.