Animal Cloning : Reprogramming the Donor Genome

Abstract

Nuclear transfer (NT) involves transferring the nucleus from a diploid cell to an unfertilized egg from which the maternal nucleus has been removed. The NT technique involves several steps. The nucleus itself can be injected or the intact cell can be transferred into the oocyte. In the latter case, the oocyte and donor cell are normally fused and the reconstructed embryo activated by an electrical pulse. The reconstructed embryos are then cultured and those that appear to be developing normally are implanted into foster mothers. The NT technique was first used to clone sheep [1, 2] and cattle [3] by using cells taken directly from early embryos. In 1995, Campbell et al. [4] produced live lambs from embryo derived cells from a ‘differentiated’ cell line that had been cultured for several weeks. In 1996, Wilmut et al. [5] created Dolly, the first animal cloned from a cell taken from an adult animal. Since then, although somatic cloned animals have been produced in several species [6–28], success rates remain low in all species, with published data showing that only 1% to 5% of reconstructed embryos result in l i ve b i r t hs ( see Ros l i n I ns t i t u te web s i t e [www.roslin.ac.uk/public/cloning.html]). Many cloned offspring die late in pregnancy or soon after birth [8, 29, 30], often from respiratory or cardiovascular dysfunction [31–33]. Abnormal placental development [34–41] is common and this is probably the major cause of fetal loss earlier in pregnancy [42]. Many of the cloned cattle and sheep that are born are much larger [29, 30, 43, 44] than normal and apparently normal clones may carry unrecognized abnormalities [45]. Differences Between Embryonic and Somatic Clones