Review

. 2018 May 22;50(5):1-10.

doi: 10.1038/s12276-018-0094-1.

The wide utility of rabbits as models of human diseases

Pedro J Esteves^{1

2

3}, Joana Abrantes⁴, Hanna-Mari Baldauf⁵, Lbachir BenMohamed^{6

7

8}, Yuxing Chen⁹, Neil Christensen¹⁰, Javier González-Gallego¹¹, Lorenzo Giacani¹², Jiafen Hu¹⁰, Gilla Kaplan¹³, Oliver T Keppler⁵, Katherine L Knight¹⁴, Xiang-Peng Kong¹⁵, Dennis K Lanning¹⁴, Jacques Le Pendu¹⁶, Ana Lemos de Matos¹⁷, Jia Liu¹⁸, Shuying Liu⁹, Ana M Lopes^{4

19}, Shan Lu⁹, Sheila Lukehart¹², Yukari C Manabe²⁰, Fabiana Neves⁴, Grant McFadden¹⁷, Ruimin Pan¹⁵, Xuwen Peng¹⁰, Patricia de Sousa-Pereira^{4

21

5}, Ana Pinheiro^{4

14}, Masmudur Rahman¹⁷, Natalie Ruvoën-Clouet¹⁶, Selvakumar Subbian²², Maria Jesús Tuñón¹¹, Wessel van der Loo⁴, Michael Vaine⁹, Laura E Via^{23

24}, Shixia Wang⁹, Rose Mage²⁵

Affiliations

¹ CIBIO, InBIO, Research Network in Biodiversity and Evolutionary Biology, Universidade do Porto, Campus de Vairão, Rua Padre Armando Quintas, 4485-661, Vairão, Portugal. pjesteves@cibio.up.pt.
² Departamento de Biologia, Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre, s/n, 4169-007, Porto, Portugal. pjesteves@cibio.up.pt.
³ Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde (CESPU), Gandra, Portugal. pjesteves@cibio.up.pt.
⁴ CIBIO, InBIO, Research Network in Biodiversity and Evolutionary Biology, Universidade do Porto, Campus de Vairão, Rua Padre Armando Quintas, 4485-661, Vairão, Portugal.
⁵ Max von Pettenkofer Institute and Gene Center, Virology, National Reference Center for Retroviruses, Faculty of Medicine, LMU München, 81377, Munich, Germany.
⁶ Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, CA, 92697, USA.
⁷ Department of Molecular Biology and Biochemistry, University of California, Irvine School of Medicine, Irvine, CA, 92697, USA.
⁸ Institute for Immunology, University of California, Irvine School of Irvine, School of Medicine, Irvine, CA, 92697, USA.
⁹ Department of Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
¹⁰ Departments of Pathology, Microbiology and Immunology, and Comparative Medicine, Penn State University, Hershey, PA, USA.
¹¹ Institute of Biomedicine (IBIOMED) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), University of León, 24071, León, Spain.
¹² Departments of Medicine and Global Health, University of Washington, Seattle, USA.
¹³ Bill and Melinda Gates Foundation, Seattle, WA, USA.
¹⁴ Department of Microbiology and Immunology, Loyola University Chicago, Maywood, IL, 60153, USA.
¹⁵ Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY10016, USA.
¹⁶ CRCINA, Inserm, Université d'Angers, Université de Nantes, Nantes, France.
¹⁷ The Biodesign Institute, Center for Immunotherapy, Vaccines, and Virotherapy, Arizona State University, Tempe, AZ, 85287-5401, USA.
¹⁸ Department of Microbiology and Immunology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, 72205, USA.
¹⁹ Department of Anatomy and Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
²⁰ Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
²¹ Departamento de Biologia, Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre, s/n, 4169-007, Porto, Portugal.
²² The Public Health Research Institute (PHRI) at New Jersey Medical School, Rutgers Biomedical and Health Sciences (RBHS), Rutgers University, Newark, NJ, USA.
²³ Tubercolosis Research Section, Laboratory of Clinical Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
²⁴ Institute of Infectious Disease and Molecular Medicine, Department of Clinical Laboratory Sciences, University of Cape Town, Cape Town, South Africa.
²⁵ Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. rmage@niaid.nih.gov.

PMID: 29789565
PMCID: PMC5964082
DOI: 10.1038/s12276-018-0094-1

Review

The wide utility of rabbits as models of human diseases

Pedro J Esteves et al. Exp Mol Med. 2018.

. 2018 May 22;50(5):1-10.

doi: 10.1038/s12276-018-0094-1.

Authors

Affiliations

¹ CIBIO, InBIO, Research Network in Biodiversity and Evolutionary Biology, Universidade do Porto, Campus de Vairão, Rua Padre Armando Quintas, 4485-661, Vairão, Portugal. pjesteves@cibio.up.pt.
² Departamento de Biologia, Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre, s/n, 4169-007, Porto, Portugal. pjesteves@cibio.up.pt.
³ Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde (CESPU), Gandra, Portugal. pjesteves@cibio.up.pt.
⁴ CIBIO, InBIO, Research Network in Biodiversity and Evolutionary Biology, Universidade do Porto, Campus de Vairão, Rua Padre Armando Quintas, 4485-661, Vairão, Portugal.
⁵ Max von Pettenkofer Institute and Gene Center, Virology, National Reference Center for Retroviruses, Faculty of Medicine, LMU München, 81377, Munich, Germany.
⁶ Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, CA, 92697, USA.
⁷ Department of Molecular Biology and Biochemistry, University of California, Irvine School of Medicine, Irvine, CA, 92697, USA.
⁸ Institute for Immunology, University of California, Irvine School of Irvine, School of Medicine, Irvine, CA, 92697, USA.
⁹ Department of Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
¹⁰ Departments of Pathology, Microbiology and Immunology, and Comparative Medicine, Penn State University, Hershey, PA, USA.
¹¹ Institute of Biomedicine (IBIOMED) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), University of León, 24071, León, Spain.
¹² Departments of Medicine and Global Health, University of Washington, Seattle, USA.
¹³ Bill and Melinda Gates Foundation, Seattle, WA, USA.
¹⁴ Department of Microbiology and Immunology, Loyola University Chicago, Maywood, IL, 60153, USA.
¹⁵ Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY10016, USA.
¹⁶ CRCINA, Inserm, Université d'Angers, Université de Nantes, Nantes, France.
¹⁷ The Biodesign Institute, Center for Immunotherapy, Vaccines, and Virotherapy, Arizona State University, Tempe, AZ, 85287-5401, USA.
¹⁸ Department of Microbiology and Immunology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, 72205, USA.
¹⁹ Department of Anatomy and Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
²⁰ Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
²¹ Departamento de Biologia, Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre, s/n, 4169-007, Porto, Portugal.
²² The Public Health Research Institute (PHRI) at New Jersey Medical School, Rutgers Biomedical and Health Sciences (RBHS), Rutgers University, Newark, NJ, USA.
²³ Tubercolosis Research Section, Laboratory of Clinical Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
²⁴ Institute of Infectious Disease and Molecular Medicine, Department of Clinical Laboratory Sciences, University of Cape Town, Cape Town, South Africa.
²⁵ Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. rmage@niaid.nih.gov.

PMID: 29789565
PMCID: PMC5964082
DOI: 10.1038/s12276-018-0094-1

Erratum in

Author Correction: The wide utility of rabbits as models of human diseases.
Esteves PJ, Abrantes J, Baldauf HM, BenMohamed L, Chen Y, Christensen N, González-Gallego J, Giacani L, Hu J, Kaplan G, Keppler OT, Knight KL, Kong XP, Lanning DK, Le Pendu J, de Matos AL, Liu J, Liu S, Lopes AM, Lu S, Lukehart S, Manabe YC, Neves F, McFadden G, Pan R, Peng X, de Sousa-Pereira P, Pinheiro A, Rahman M, Ruvoën-Clouet N, Subbian S, Tuñón MJ, van der Loo W, Vaine M, Via LE, Wang S, Mage R. Esteves PJ, et al. Exp Mol Med. 2019 Jul 4;51(7):1. doi: 10.1038/s12276-019-0252-0. Exp Mol Med. 2019. PMID: 31270317 Free PMC article.

Abstract

Studies using the European rabbit Oryctolagus cuniculus contributed to elucidating numerous fundamental aspects of antibody structure and diversification mechanisms and continue to be valuable for the development and testing of therapeutic humanized polyclonal and monoclonal antibodies. Additionally, during the last two decades, the use of the European rabbit as an animal model has been increasingly extended to many human diseases. This review documents the continuing wide utility of the rabbit as a reliable disease model for development of therapeutics and vaccines and studies of the cellular and molecular mechanisms underlying many human diseases. Examples include syphilis, tuberculosis, HIV-AIDS, acute hepatic failure and diseases caused by noroviruses, ocular herpes, and papillomaviruses. The use of rabbits for vaccine development studies, which began with Louis Pasteur's rabies vaccine in 1881, continues today with targets that include the potentially blinding HSV-1 virus infection and HIV-AIDS. Additionally, two highly fatal viral diseases, rabbit hemorrhagic disease and myxomatosis, affect the European rabbit and provide unique models to understand co-evolution between a vertebrate host and viral pathogens.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

**Fig. 1. Structural characteristics of rabbit antibodies.**
a Crystal structure of rabbit anti-HIV-1 gp120 V3 monoclonal antibody R56 (PDB ID 4JO1). R56 is used here as an example of typical rabbit antibodies. Rabbit kappa chain often has a disulfide bond linking its VL and CL1 regions, limiting the flexibility of the Fab elbow. This disulfide bond may contribute to the stability of rabbit antibodies in general. Additionally, non-canonical disulfide bonds are often observed in CDR loops of rabbit antibodies. R56 has two disulfide bonds in its antigen bonding site. b Details of the elbow kappa chain disulfide bond. c Details of the R56 antigen-binding site, with its V3 epitope shown in magenta

**Fig. 2. Infected and non-infected rabbit eyes.**
Eyes of 8-week-old New Zealand White (NZW) female rabbits on day 35 after ocular infection with HSV-1 (2 × 10⁵ pfu/eye of strain *McKrae*). Eye pictures were taken under regular light

See this image and copyright information in PMC

References

1. Pasteur L. Méthode pour prévenir la rage après morsure. Comptes rendus Hebd. Des. séances De. l’Académie Des. Sci. 1885;101:765–774.
1. Pinheiro A, et al. Molecular bases of genetic diversity and evolution of the immunoglobulin heavy chain variable region (IGHV) gene locus in leporids. Immunogenetics. 2011;63:397–408. - PMC - PubMed
1. Pinheiro A, et al. An overview of the lagomorph immune system and its genetic diversity. Immunogenetics. 2016;68:83–107. - PubMed
1. Mage RG, Pinheiro A, Lemos de Matos A, Esteves PJ. The immune system of lagomorphs. In: Ratcliffe MJH, editor. Encyclopedia of immunobiology. Amsterdam, Holand: Elsevier; 2016. pp. 515–525.
1. Burkholder TH, Linton GFR, Hoyt J, Young R. The rabbit as an experimental model. In: Suckow MA, Stevens KA, Wilson RP, editors. The laboratory rabbit, guinea pig, hamster, and other rodents. Cambridge, MA, USA: Academic Press; 2012. pp. 529–560.

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The wide utility of rabbits as models of human diseases

Affiliations

The wide utility of rabbits as models of human diseases

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources