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ABSTRACT It is over a decade since the first demonstration that mouse embryonic stem cells could be used to transfer a predetermined genetic modification to a whole animal1. The extension of
this technique to other mammalian species, particularly livestock, might bring numerous biomedical benefits, for example, ablation of xenoreactive transplantation antigens, inactivation of
genes responsible for neuropathogenic disease and precise placement of transgenes designed to produce proteins for human therapy. Gene targeting has not yet been achieved in mammals other
than mice, however, because functional embryonic stem cells have not been derived. Nuclear transfer from cultured somatic cells provides an alternative means of cell-mediated
transgenesis2,3. Here we describe efficient and reproducible gene targeting in fetal fibroblasts to place a therapeutic transgene at the ovine α1(I) procollagen (_COL1A1_) locus and the
production of live sheep by nuclear transfer. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access
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subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS AN OPTIMIZED CULTURE SYSTEM FOR EFFICIENT DERIVATION OF PORCINE EXPANDED POTENTIAL STEM CELLS
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references ACKNOWLEDGEMENTS We would like to acknowledge the contributions of Y. Gibson and K. Mycock for embryo manipulation; E. Emslie and L. Hutchison for molecular biology technical
assistance; T. Johnston for protein analysis; and the PPL Therapeutics large animal team for animal husbandry and veterinary procedures. We thank I. Garner and D. Ayares for useful
discussions. AUTHOR INFORMATION Author notes * K. H. S. Campbell Present address: Division of Animal Physiology, University of Nottingham, School of Biological Sciences, Loughborough, LE12
5RD, UK * Correspondence and requests for materials should be addressed to A.J.K. AUTHORS AND AFFILIATIONS * PPL Therapeutics Ltd, Roslin, Edinburgh, EH25 9PP, UK K. J. McCreath, J.
Howcroft, K. H. S. Campbell, A. Colman, A. E. Schnieke & A.J. Kind Authors * K. J. McCreath View author publications You can also search for this author inPubMed Google Scholar * J.
Howcroft View author publications You can also search for this author inPubMed Google Scholar * K. H. S. Campbell View author publications You can also search for this author inPubMed Google
Scholar * A. Colman View author publications You can also search for this author inPubMed Google Scholar * A. E. Schnieke View author publications You can also search for this author
inPubMed Google Scholar * A.J. Kind View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to A.J. Kind. RIGHTS AND
PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE McCreath, K., Howcroft, J., Campbell, K. _et al._ Production of gene-targeted sheep by nuclear transfer from
cultured somatic cells. _Nature_ 405, 1066–1069 (2000). https://doi.org/10.1038/35016604 Download citation * Received: 28 January 2000 * Accepted: 05 May 2000 * Issue Date: 29 June 2000 *
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