Genome engineering technologies in rabbits

Song, Jun; Zhang, Jifeng; Xu, Jie; Garcia-Barrio, Minerva T.; Chen, Y. Eugene; Yang, Dongshan

doi:10.7555/jbr.34.20190133

Cited by 11 publications

(8 citation statements)

References 129 publications

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“…In particular, the CRISPR/Cas9 mediated genome editing technique is a powerful tool to generate genetically modified animals. Recently, the detail of genome engineering technologies in rabbits was well reviewed by Song et al [42].…”

Section: Traditional Pronuclear Microinjection To Generate Transgenic Rabbitsmentioning

confidence: 99%

Transgenic Rabbit Models: Now and the Future

et al. 2020

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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.

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Section: Traditional Pronuclear Microinjection To Generate Transgenic Rabbitsmentioning

confidence: 99%

Transgenic Rabbit Models: Now and the Future

et al. 2020

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“…The rabbit (Oryctolagus Cuniculus) is a classic laboratory animal model species and is increasingly becoming a translational model of choice for bridging the gap between rodent models and larger animal models [62][63][64][65][66][67][68][69][70][71]. The method to produce transgenic rabbits by pronuclear microinjection is well-established and comprehensively described [72].…”

Section: The Birth Of Immunodeficient Rabbitsmentioning

confidence: 99%

Immunodeficient Rabbit Models: History, Current Status and Future Perspectives

et al. 2020

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Production of immunodeficient (ID) models in non-murine animal species had been extremely challenging until the advent of gene-editing tools: first zinc finger nuclease (ZFN), then transcription activator-like effector nuclease (TALEN), and most recently clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR)/Cas9. We and others used those gene-editing tools to develop ID rabbits carrying a loss of function mutation in essential immune genes, such as forkhead box protein N1 (FOXN1), recombination activating gene 1/2 (RAG1/2), and interleukin 2 receptor subunit gamma (IL2RG). Like their mouse counterparts, ID rabbits have profound defects in their immune system and are prone to bacterial and pneumocystis infections without prophylactic antibiotics. In addition to their use as preclinical models for primary immunodeficient diseases, ID rabbits are expected to contribute significantly to regenerative medicine and cancer research, where they serve as recipients for allo- and xeno-grafts, with notable advantages over mouse models, including a longer lifespan and a much larger body size. Here we provide a concise review of the history and current status of the development of ID rabbits, as well as future perspectives of this new member in the animal model family.

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“…For example, it can be employed to generate gene knockout and knock-in animals as disease models. Our team has established a robust platform in generating knockout and knock-in rabbit models (Yang et al, 2014;Song et al, 2016;Yang et al, 2016;Song et al, 2017;Yang et al, 2019;Song et al, 2020). Furthermore, CRISPR/Cas9 can be used to correct disease causing mutations hence holds the promise for gene editing based therapeutics.…”

Section: Introductionmentioning

confidence: 99%

Production of CFTR-ΔF508 Rabbits

et al. 2021

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Cystic Fibrosis (CF) is a lethal autosomal recessive disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). The most common mutation is the deletion of phenylalanine residue at position 508 (ΔF508). Here we report the production of CFTR-ΔF508 rabbits by CRISPR/Cas9-mediated gene editing. After microinjection and embryo transfer, 77 kits were born, of which five carried the ΔF508 mutation. To confirm the germline transmission, one male ΔF508 founder was bred with two wild-type females and produced 16 F1 generation kits, of which six are heterozygous ΔF508/WT animals. Our work adds CFTR-ΔF508 rabbits to the toolbox of CF animal models for biomedical research.

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Genome engineering technologies in rabbits

Cited by 11 publications

References 129 publications

Transgenic Rabbit Models: Now and the Future

Transgenic Rabbit Models: Now and the Future

Immunodeficient Rabbit Models: History, Current Status and Future Perspectives

Production of CFTR-ΔF508 Rabbits

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