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Mammalian cloning: advances and limitations

Nature Reviews Genetics volume 1, pages 199–207 (2000)Cite this article

Abstract

For many years, researchers cloning mammals experienced little success, but recent advances have led to the successful cloning of several mammalian species. However, cloning by the transfer of nuclei from adult cells is still a hit-and-miss procedure, and it is not clear what technical and biological factors underlie this. Our understanding of the molecular basis of reprogramming remains extremely limited and affects experimental approaches towards increasing the success rate of cloning. Given the future practical benefits that cloning can offer, the time has come to address what should be done to resolve this problem.

Key Points

  • Several mammalian species have been cloned by transferring nuclei from various adult somatic cells into enucleated oocytes.

  • The cloning procedure is still inefficient, and only one in a hundred of manipulated oocytes develop to adulthood.

  • Reasons for the low efficiency of cloning are largely unknown and are probably both technical and biological.

  • The incomplete or incorrect reprogramming of the donor nuclear genome — its inability to completely adapt and function in the new environment — is the most significant factor contributing to low cloning efficiency.

  • The cloning of large farm animals from genetically manipulated donor nuclei will have significant practical benefits.

  • The cloning of humans is prohibited because of safety reasons at present. However, therapeutic cloning and the production of individualized human embryonic stem cells for use in cell- and tissue-replacement therapies may have great importance in human medicine.

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Figure 1: Current nuclear-transfer procedures.
Figure 2: Serial nuclear transfer34.
Figure 3: The first mouse cloned from an adult somatic (cumulus) cell.
Figure 4: The behaviour of a nuclear donor following its transfer into an enucleated oocyte.

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Acknowledgements

I would like to thank Professor Ryuzo Yanagimachi from the University of Hawaii for kindly giving permission to reproduce Figures 3 and 4.

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Authors and Affiliations

  1. Max-Planck Institute of Immunobiology, Stübeweg 51, Freiburg, 79108, Germany

    Davor Solter

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  1. Davor Solter
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DATABASE LINKS

Inositol-1,4,5-trisphosphate receptor

FURTHER INFORMATION

In his Image: The Cloning of a Man

Roslin institute

European ban on human cloning

United States National Bioethics Advisory Commission's recommendations

ENCYCLOPEDIA OF LIFE SCIENCES

Nuclear transfer from established cell lines

Imprinting in mammals

Cleavage and gastrulation in mouse embryos

Sperm-egg binding in mammals

Glossary

CLONING EFFICIENCY

Cloning efficiency is calculated from the percentage of manipulated embryos that develops to adulthood, and reflects how successful or not a cloning experiment has been.

THERAPEUTIC CLONING

The use of nuclear transfer to produce individually tailored human embryonic stem cells for tissue- and cell-replacement therapies.

KARYOPLAST

An isolated donor nucleus, together with its envelope of cytoplasm and plasma membrane.

CYTOPLAST

Enucleated oocyte or embryo (zygote) that is used as a nuclear recipient.

POLAR BODY

The structure that is extruded from the oocyte during meiosis, which contains one haploid set of chromosomes.

BIOREACTORS

Animals that are genetically engineered to produce proteins or macromolecules that are of use in human medicine.

CYTOKINESIS

The division of the cytoplasm of a parent cell into daughter cells after nuclear division.

OOCYTE ACTIVATION

This occurs when the binding of sperm to the egg cell membrane triggers a series of responses in the oocyte that prepare the oocyte for fertilization and block the entry of more sperm.

CALCIUM TRANSIENTS

A series of repetitive oscillations in calcium concentration that move across the egg cytoplasm following sperm entry, which are essential for egg activation.

MITOCHONDRIAL HETEROPLASMY

The presence of more than one type of mitochondrial DNA within the same cell.

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Solter, D. Mammalian cloning: advances and limitations. Nat Rev Genet 1, 199–207 (2000). https://doi.org/10.1038/35042066

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