Abstract

Transgenic rabbits have contributed to the progress of biomedical science as human disease models because of their unique features, such as the lipid metabolism system similar to humans and medium body size that facilitates handling and experimental manipulation. In fact, many useful transgenic rabbits have been generated and used in research fields such as lipid metabolism and atherosclerosis, cardiac failure, immunology, and oncogenesis. However, there have been long-term problems, namely that the transgenic efficiency when using pronuclear microinjection is low compared with transgenic mice and production of knockout rabbits is impossible owing to the lack of embryonic stem cells for gene targeting in rabbits. Despite these limitations, the emergence of novel genome editing technology has changed the production of genetically modified animals including the rabbit. We are finally able to produce both transgenic and knockout rabbit models to analyze gain- and loss-of-functions of specific genes. It is expected that the use of genetically modified rabbits will extend to various research fields. In this review, we describe the unique features of rabbits as laboratory animals, the current status of their development and use, and future perspectives of transgenic rabbit models for human diseases.

Highlights

  • Modified animals can be very useful tools for biomedical research

  • We introduce the unique features of the rabbit as a laboratory animal, the current status of their development and use, and future perspectives of transgenic rabbit models for human diseases

  • The characteristic details of transgenic rabbit models for lipid metabolism and atherosclerosis have been described in several reviews [3,7,8]

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Summary

Introduction

Modified animals can be very useful tools for biomedical research. They are defined animals whose DNA has been altered using genetic engineering techniques, which include transgenic (carrying exogenous gene), knockout (disrupted endogenous gene by gene targeting), and knock-in (inserted gene sequence at a particular locus by gene targeting). In comparison with mice, the transgenic efficiency when using pronuclear microinjection is low and the production of knockout rabbits is difficult because ES cells have not been established for gene targeting in the rabbit [8,11]. These problems limit the use of genetically modified rabbits as human disease models. 9 (Cas9), have changed production of genetically modified animals including the rabbit [19,20,21] These techniques have revolutionized gene engineering technology because knockout animals can be produced with high efficiency by these techniques without ES cells. We introduce the unique features of the rabbit as a laboratory animal, the current status of their development and use, and future perspectives of transgenic rabbit models for human diseases

General Features of the Laboratory Rabbits
Traditional Pronuclear Microinjection to Generate Transgenic Rabbits
Transgenic Rabbits for Human Disease Models
Transgenic Rabbit as a Bioreactor
Findings
Conclusions and Future Perspectives
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