Immunodeficient Rabbit Models: History, Current Status and Future Perspectives

Song, Jun; Pallas, Brooke; Yang, Dongshan; Zhang, Jifeng; Agarwal, Yash; Chen, Y. Eugene; Bility, Moses; Xu, Jie

doi:10.3390/app10207369

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Immunodeficient Rabbit Models: History, Current Status and Future Perspectives

by

Jun Song

¹

,

Brooke Pallas

^1,2,

Dongshan Yang

¹,

Jifeng Zhang

¹

,

Yash Agarwal

³,

Y. Eugene Chen

¹,

Moses Bility

^3,* and

Jie Xu

^1,*

¹

Center for Advanced Models and Translational Sciences and Therapeutics, University of Michigan, Ann Arbor, MI 48109, USA

²

Unit for Laboratory Animal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA

³

Department of Infectious Diseases and Microbiology, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Public Health, Pittsburgh, PA 15261, USA

^*

Authors to whom correspondence should be addressed.

Appl. Sci. 2020, 10(20), 7369; https://doi.org/10.3390/app10207369

Submission received: 16 September 2020 / Revised: 17 October 2020 / Accepted: 18 October 2020 / Published: 21 October 2020

(This article belongs to the Special Issue Rabbit Models for Translational Medicine)

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Abstract

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.

Keywords: immunodeficient rabbits; gene editing; animal models

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MDPI and ACS Style

Song, J.; Pallas, B.; Yang, D.; Zhang, J.; Agarwal, Y.; Chen, Y.E.; Bility, M.; Xu, J. Immunodeficient Rabbit Models: History, Current Status and Future Perspectives. Appl. Sci. 2020, 10, 7369. https://doi.org/10.3390/app10207369

AMA Style

Song J, Pallas B, Yang D, Zhang J, Agarwal Y, Chen YE, Bility M, Xu J. Immunodeficient Rabbit Models: History, Current Status and Future Perspectives. Applied Sciences. 2020; 10(20):7369. https://doi.org/10.3390/app10207369

Chicago/Turabian Style

Song, Jun, Brooke Pallas, Dongshan Yang, Jifeng Zhang, Yash Agarwal, Y. Eugene Chen, Moses Bility, and Jie Xu. 2020. "Immunodeficient Rabbit Models: History, Current Status and Future Perspectives" Applied Sciences 10, no. 20: 7369. https://doi.org/10.3390/app10207369

APA Style

Song, J., Pallas, B., Yang, D., Zhang, J., Agarwal, Y., Chen, Y. E., Bility, M., & Xu, J. (2020). Immunodeficient Rabbit Models: History, Current Status and Future Perspectives. Applied Sciences, 10(20), 7369. https://doi.org/10.3390/app10207369

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Immunodeficient Rabbit Models: History, Current Status and Future Perspectives

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