Genetically modified rabbit models for cardiovascular medicine

Genetically modified (GM) rabbits are outstanding animal models for studying human genetic and acquired diseases. As such, GM rabbits that express human genes have been extensively used as models of cardiovascular disease. Rabbits are genetically modified via prokaryotic microinjection. Through this process, genes are randomly integrated into the rabbit genome. Moreover, gene targeting in embryonic stem (ES) cells is a powerful tool for understanding gene function. However, rabbits lack stable ES cell lines. Therefore, ES-dependent gene targeting is not possible in rabbits. Nevertheless, the RNA interference technique is rapidly becoming a useful experimental tool that enables researchers to knock down specific gene expression, which leads to the genetic modification of rabbits. Recently, with the emergence of new genetic technology, such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), clustered regularly interspaced short palindromic repeats (CRISPR), and CRISPR-associated protein 9 (CRISPR/Cas9), major breakthroughs have been made in rabbit gene targeting. Using these novel genetic techniques, researchers have successfully modified knockout (KO) rabbit models. In this paper, we aimed to review the recent advances in GM technology in rabbits and highlight their application as models for cardiovascular medicine.