Bioscientifica Proceedings

A tremendous amount is required of the oocyte cytoplasm to reprogramme a differentiated donor nucleus after somatic cell nuclear transfer so that it re-acquires a state of totipotency and can form a cloned individual. These reprogramming events must occur in a relatively short period after embryo reconstruction, quite unlike the situation during gametogenesis. It is remarkable that nuclear transfer can produce physiologically normal animals, but the process is highly prone to epigenetic errors. Aberrant patterns of gene expression are believed to contribute to the cumulative losses and abnormal phenotypes observed throughout development, from embryonic to adult stages. As a consequence, cloning efficiencies with current nuclear transfer technology are low and limit practical applications in farming. These applications depend upon the reliability with which nuclear transfer can reproduce specific genotypes and phenotypes in resulting offspring. Present animal welfare issues are a significant barrier for acceptance of nuclear transfer in agriculture. Any long lasting effects from cloning, as revealed in some mouse studies, need to be comprehensively evaluated in cloned livestock. The safety of food products derived from clones also needs to be thoroughly evaluated. The current indication that the sexually derived offspring of nuclear transfer clones are normal provides confidence for the first applications of the technology in agriculture, namely the generation of cloned, genetically elite animals for subsequent breeding. Future improvements in cloning will come from both technical advances and a greater fundamental understanding of the molecular mechanisms of reprogramming with an aim to control this process better. Increased efficiencies should improve the acceptability and utility of cloning technology.

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