A simple adeno-associated virus-based approach for the generation of cardiac genetic models in rats [version 1; peer review: 2 approved]

• Published in: F1000 research Vol. 9; p. 1441
• Main Authors: Schlesinger-Laufer, Michal, Douvdevany, Guy, Haimovich-Caspi, Lilac, Zohar, Yaniv, Shofty, Rona, Kehat, Izhak
• Format: Journal Article
• Language: English
• Published: England Faculty of 1000 Ltd 2020; F1000 Research Limited; F1000 Research Ltd
• Subjects: Animal models; Animal welfare; Animals; Calcium-binding protein; Cardiovascular disease; Cardiovascular diseases; Congestive heart failure; Coronary artery disease; Dependovirus - genetics; Disease Models, Animal; Drug development; Genetic Vectors; Genomes; Heart failure; Heart Failure - genetics; Heart rate; Histology; Hypertrophy; Injection; Laboratories; Method; Mortality; Neonates; Physiology; Plasmids; Promoter Regions, Genetic; Rats; Rats, Transgenic; Toxicity; Transgenes; Troponin; Troponin T; Troponin T - genetics; Israel; Cardiac research; animal models; Adeno-associated virus
• ISSN: 2046-1402; 2046-1402
• DOI: 10.12688/f1000research.27675.1

Background: Heart failure is a major health problem and progress in this field relies on better understanding of the mechanisms and development of novel therapeutics using animal models. The rat may be preferable to the mouse as a cardiovascular disease model due to its closer physiology to humans and due to its large size that facilitates surgical and monitoring procedures. However, unlike the mouse, genetic manipulation of the rat genome is challenging. Methods: Here we developed a simple, refined, and robust cardiac-specific rat transgenic model based on an adeno-associated virus (AAV) 9 containing a cardiac troponin T promoter. This model uses a single intraperitoneal injection of AAV and does not require special expertise or equipment. Results: We characterize the AAV dose required to achieve a high cardiac specific level of expression of a transgene in the rat heart using a single intraperitoneal injection to neonates. We show that at this AAV dose GFP expression does not result in hypertrophy, a change in cardiac function or other evidence for toxicity. Conclusions: The model shown here allows easy and fast transgenic based disease modeling of cardiovascular disease in the rat heart, and can also potentially be expanded to deliver Cas9 and gRNAs or to deliver small hairpin (sh)RNAs to also achieve gene knockouts and knockdown in the rat heart.