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Transgenic rabbit models for cardiac disease research
Author(s) -
Hornyik Tibor,
Rieder Marina,
Castiglione Alessandro,
Major Peter,
Baczko Istvan,
Brunner Michael,
Koren Gideon,
Odening Katja E.
Publication year - 2022
Publication title -
british journal of pharmacology
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.15484
Subject(s) - disease , heart disease , crispr , neuroscience , cardiac electrophysiology , transgene , heart development , microinjection , cardiovascular physiology , genetically modified mouse , cardiomyopathy , genome editing , cardiac function curve , biology , heart failure , bioinformatics , medicine , computational biology , pathology , cardiology , electrophysiology , genetics , embryonic stem cell , gene
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. LINKED ARTICLES: This article is part of a themed issue on Preclinical Models for Cardiovascular disease research (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.5/issuetoc.