International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


Ian Wilmut
Roslin Institute
Midlothian EH25 9PS UK

The production of cloned offspring by nuclear transfer is still a very inefficient process with only 1-4% of reconstructed embryo developing to become viable offspring. This outcome is similar for all 5 species in which somatic cell nuclear transfer has been achieved, regardless of species, donor cell type or method of nuclear transfer. However, the precise stage when loss occurs may vary between different cell types. The low overall efficiency is the cumulative result of failure at all stages of development through from cleavage to the post-natal period. The unusually high loss, spread throughout development is assumed to reflect the inappropriate expression of a number of genes whose lethal effects are exerted at different stages of development. Both direct and indirect evidence is accumulating of errors in expression of imprinted genes, but this does not indicate that these genes are the only ones to be expressed inappropriately. At present very little is known of the molecular mechanisms involved in either the "reprogramming" of gene expression or the causes of death of cloned embryos. Significant improvements in the efficiency of nuclear transfer may depend upon modifications to the procedure to enhance the ability of the oocyte cytoplasm to remodel the chromatin of the transferred nucleus and achieve appropriate developmental regulation of gene expression.

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