Cloning Animals by Nuclear Transplantation

CLONING ANIMALS BY NUCLEAR TRANSPLANTATION

Although the cloning of Dolly the sheep in 1996 created a major furor in the media, from a scientific viewpoint it was a relatively small step in a developing technology. Cloning animals relies on the technique of nuclear transplantation. This actually dates back to 1952 when nuclei from early frog embryos were transplanted into eggs from which the nucleus had previously been removed. Some attempts gave rise to normal embryos. Although animal somatic cells differentiate and eventually become irreversibly committed to specialized roles, their nuclei nonetheless retain a complete genome. (A few exceptions, such as red blood cells, lose their nucleus.) Under some circumstances the cytoplasmic environment in the egg cell can reprogram nuclei from somatic cells. Not surprisingly, the earlier the stage of development in the nuclei, the easier they are to reprogram.

Nuclear transplantation can be used to generate a group of identical cloned animals. Several nuclei from the same donor are transplanted into a series of enucleated eggs. Since the 1980s, nuclear transfer in a variety of mammals has been performed successfully using nuclei from early embryos (morula or blastocyst stages). Fusing a somatic cell with an empty egg cell transfers the donor nucleus into a completely nondifferentiated cytoplasm. A brief electrical pulse fuses the two cell membranes into one embryo. In 1995, nuclei from cultured embryonic cells of sheep were successfully transplanted. Two lambs, Megan and Morag, were produced by this technique at the Roslin Institute in Edinburgh, Scotland. In 1996 the same research group produced Dolly by nuclear transplantation from an adult cell line—the epithelial layer of the mammary gland. Thus Dolly was the first mammal to be produced using a nucleus from a differentiated cell line.