Nuclear transplantation

The science of the lambs

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First Dolly, now Polly! In the 19 December issue of Science (278, 2130-2133; 1997), Angelika Schnieke and colleagues describe the generation of transgenic lambs using nuclear transfer — the technique that they developed to generate Dolly the sheep (Wilmut, I. et al. Nature 385, 810–813; 1997). Credit: ROSLIN INSTITUTE, EDINBURGH

But that's only half the story. The authors have created six lambs, including one called Polly (pictured), that should be able to produce milk containing factor IX — the blood-clotting protein that is deficient in people with haemophilia B. Not only do these results highlight the commercial potential of nuclear transfer, but they pave the way for its use in understanding other diseases.

Dolly was created by fusing the DNA of an adult udder cell with an egg from which the DNA had been removed. To make Polly and her sisters, Schnieke et al. used fetal fibroblast cells containing a transgene designed to express factor IX in the milk of the sheep and/or a selectable marker. After fusion with this DNA, the eggs were implanted in surrogate Scottish Blackface ewes. Three of the resulting lambs contained the marker only, but the other three also carried the transgene.

Until now, the only way to produce transgenic animals has been by pronuclear injection. Between 200 and 300 copies of a transgene are introduced into a just-fertilized egg, and this is then implanted into a surrogate mother. But only around two per cent of the animals express the gene, and just a fraction of these produce commercially viable amounts of protein.

When Polly begins to produce factor IX, large quantities should be obtainable at low cost, and the protein will be free from the risks associated with purification from human plasma. Yields will be restricted only by the other (sheep) proteins in the milk, and a next step will be to try and knock out the genes that code for these. So Polly could be the first of many lines of transgenic sheep — and, as with Dolly, the crowds will undoubtedly flock to see her.

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