Large animal Models of rarae genetic disorders_Orphanet J of Rare Diseases_J McEwan.pdf (625.42 kB)

Large animal models of rare genetic disorders: Sheep as phenotypically relevant models of human genetic disease

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posted on 2023-05-03, 15:05 authored by Ashish R. Pinnapureddy, Cherie Stayner, John McEwanJohn McEwan, Olivia Baddeley, John Forman, Muchael R. Eccles
Animals that accurately model human disease are invaluable in medical research, allowing a critical understanding of disease mechanisms, and the opportunity to evaluate the effect of therapeutic compounds in pre-clinical studies. Many types of animal models are used world-wide, with the most common being small laboratory animals, such as mice. However, rodents often do not faithfully replicate human disease, despite their predominant use in research. This discordancy is due in part to physiological differences, such as body size and longevity. In contrast, large animal models, including sheep, provide an alternative to mice for biomedical research due to their greater physiological parallels with humans. Completion of the full genome sequences of many species, and the advent of Next Generation Sequencing (NGS) technologies, means it is now feasible to screen large populations of domesticated animals for genetic variants that resemble human genetic diseases, and generate models that more accurately model rare human pathologies. In this review, we discuss the notion of using sheep as large animal models, and their advantages in modelling human genetic disease. We exemplify several existing naturally occurring ovine variants in genes that are orthologous to human disease genes, such as the Cln6 sheep model for Batten disease. These, and other sheep models, have contributed significantly to our understanding of the relevant human disease process, in addition to providing opportunities to trial new therapies in animals with similar body and organ size to humans. Therefore sheep are a significant species with respect to the modelling of rare genetic human disease, which we summarize in this review.


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© 2015 Pinnapureddy et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.


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BioMed Central

Journal title

Orphanet Journal of Rare Diseases




Pinnapureddy, A. R., Stayner, C., McEwan, J., Baddeley, O., Forman, J., & Eccles, M. R. (2015). Large animal models of rare genetic disorders: sheep as phenotypically relevant models of human genetic disease. Orphanet Journal of Rare Diseases, 10, 107. doi:10.1186/s13023-015-0327-5

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