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Cloned lambs—lessons from pathology

Nature Biotechnology volume 21, pages 744–745 (2003)Cite this article

Significant losses are associated with the generation of cloned animals. Although it is becoming clear that placental abnormalities result in many of the losses in early gestation, less emphasis has been placed on understanding the mechanisms responsible for clone deaths in the perinatal period. In contrast to the opinion that the majority of cloned animals are 'seemingly healthy'1, we provide here an alternative view on the basis of a detailed pathological study of a group of cloned lambs that were not viable after birth. Our analysis reveals new evidence of a series of cloning-related abnormalities (summarized in Table 1). These findings provide a foundation for analysis of the mechanisms of late-clone failure and raise the as-yet unanswered question of whether more subtle expression of the defects could be present in surviving clones that are apparently normal. Only thorough pathological analysis is likely to satisfactorily answer such a question.

Table 1 Summary of physical features and pathology of failed neonatal cloned sheep
Full size table

To date, most cloning defects have been viewed as isolated incidents, or amalgamated into one category of 'large offspring syndrome'—a syndrome occurring in association with embryo manipulation and characterized by large size at birth plus a range of other poorly defined morphological abnormalities2. Our detailed analysis of late-clone defects has revealed many different types of defects, some of which have parallels with congenital human diseases.

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Acknowledgements

The authors would like to thank A. Dawson, N. MacIntyre, S. Moss, J. Bracken, J. Bowering, W. Bosma, P. Johnston, D. McGavin, W. Ritchie, M. Ritchie, A. Travers, C. Denning, J. Fletcher, A. Ainslie and T. Ferrier for technical support. Part of this study was funded by the Geron Corporation (Menlo Park, CA, USA). This study was conducted following approval by Roslin Institute's Animal Ethics Committee and within a project license issued under the Animal (Scientific Procedures) Act 1986.

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  1. the University of Edinburgh, Veterinary Pathology, Easter Bush Veterinary Centre, Roslin, EH25 9RG, Midlothian, UK

    Susan M Rhind

  2. the Roslin Institute, Roslin, EH25 9PS, Midlothian, UK

    Tim J King, Linda M Harkness, Paul DeSousa & Ian Wilmut

  3. the University of Edinburgh, Pathology, Medical School, Teviot Place, EH8 9AG, Edinburgh, UK

    Chris Bellamy & William Wallace

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Rhind, S., King, T., Harkness, L. et al. Cloned lambs—lessons from pathology. Nat Biotechnol 21, 744–745 (2003). https://doi.org/10.1038/nbt0703-744

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