Production of gene-targeted sheep by nuclear transfer from cultured somatic cells
rcjohnsen at aol.com
Sat Jul 8 12:58:15 EST 2000
Nature 405, 1066 - 1069 (2000) © Macmillan Publishers Ltd.
Production of gene-targeted sheep by nuclear transfer from cultured somatic
K. J. MCCREATH, J. HOWCROFT, K. H. S. CAMPBELL*, A. COLMAN, A. E. SCHNIEKE &
PPL Therapeutics Ltd, Roslin, Edinburgh, EH25 9PP, UK
* Present address: University of Nottingham, School of Biological Sciences,
Division of Animal Physiology, Loughborough, LE12 5RD, UK
Correspondence and requests for materials should be addressed to A.J.K.
(e-mail: akind at ppl-therapeutics.com).
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 1(I) procollagen (COL1A1) locus and
the production of live sheep by nuclear transfer.
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