Somatic cell nuclear transfer
J. R. HillCSIRO Livestock Industries, Chiswick, New England Highway, Armidale, NSW 2350, Australia. Email: Jon.Hill@csiro.au
Australian Journal of Experimental Agriculture 44(11) 1101-1104 https://doi.org/10.1071/EA03234
Submitted: 16 November 2003 Accepted: 20 September 2004 Published: 14 December 2004
Abstract
Nuclear transfer research became front-page news when the birth of Dolly, the cloned ewe, was reported by Ian Wilmut and Keith Campbell in 1997. Since Dolly’s birth, offspring from many other species have been produced using somatic cell nuclear transfer. While Dolly’s birth transformed embryology research, her death in February 2003 marked the beginning of the next phase of research and development. This period will determine the scale of the commercial and societal benefits that accrue from somatic cell nuclear transfer and transgenics.
Proof of concept for many of the potential benefits of somatic cell nuclear transfer has already been demonstrated. Desirable genotypes have been cloned, further insights into the nuclear reprogramming process have been achieved, and precision gene insertions/deletion has been demonstrated.
It is likely that nuclear transfer can be adapted to ‘copy’ individuals from any mammalian species. Offspring have been produced using cells from sheep, mice, cattle, goats, pigs, rabbits and a cat. It appears very likely that copying of other species such as horses will follow shortly. However, early results from monkeys suggest that somatic cell nuclear transfer in primates may require further intensive study before the likelihood of success can be predicted. The nuclear transfer process is far less efficient at producing healthy offspring than the natural process of combining a sperm with an egg. Fewer normal embryos, fetuses and offspring are produced from somatic cell nuclear transfer than from other assisted breeding techniques. The reasons for this appear to be related to abnormal expression of key developmental genes. Many of these genes are imprinted genes, which rely on correct methylation patterns of the genome that are established in the first week of life. Research into this area not only aids further development of the nuclear transfer technique but is also important for basic research into understanding the nuclear reprogramming process in mammals.
The combination of nuclear transfer with gene insertion/deletion techniques has permitted a quantum leap in the efficiency of producing livestock with an additional ‘value adding’ gene. This has resulted in more economical production of animals that carry a specific valuable gene, such as a gene to enable production of novel or valuable proteins in their milk. Precision gene insertions or deletions will become more available in the near term so that this technique will become as important for testing gene function for agricultural applications as it is in mice for biomedical uses.
Our challenge for the next decade is to fine-tune the somatic cell nuclear transfer technique so as to achieve more normal development rates. At the same time we need to increase the efficiency of targeted gene insertion or deletion so that the 2 techniques can be effectively combined to utilise the information on gene function created by livestock gene discovery programs.
Baguisi A,
Behboodi E,
Melican DT,
Pollock JS, Destrempes MM , et al.
(1999) Production of goats by somatic cell nuclear transfer. Nature Biotechnology 17, 456–461.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Betts DH,
Bordignon V,
Hill JR,
Winger QA,
Westhusin ME,
Smith LC, Kind AJ
(2001) Reprogramming of telomerase activity and rebuilding of telomere length in cloned cattle. Proceedings of the National Academy of Sciences of the United States of America 98, 1077–1082.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Boiani M,
Eckardt S,
Scholer HR, McLaughlin KJ
(2002) Oct4 distribution and level in mouse clones: consequences for pluripotency. Genes and Development 16, 1209–1219.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Chavatte-Palmer P,
Heyman Y, Renard JP
(2000) Cloning and associated physiopathology of gestation. Gynecologie, Obstetrique and Fertilite 28, 633–642.
Chesne P,
Adenot PG,
Viglietta C,
Baratte M,
Boulanger L, Renard JP
(2002) Cloned rabbits produced by nuclear transfer from adult somatic cells. Nature Biotechnology 20, 366–369.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Cibelli JB,
Stice SL,
Golueke PJ,
Kane JJ,
Jerry J,
Blackwell C,
Ponce de Leon FA, Robl JM
(1998) Cloned transgenic calves produced from nonquiescent fetal fibroblasts. Science 280, 1256–1258.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Daniels R,
Hall V, Trounson AO
(2000) Analysis of gene transcription in bovine nuclear transfer embryos reconstructed with granulosa cell nuclei Biology of Reproduction 63, 1034–1040.
| PubMed |
De Sousa PA,
Winger QA,
Hill JR,
Jones K,
Watson AJ, Westhusin ME
(1999) Reprogramming of fibroblast nuclei after transfer into bovine oocytes. Cloning 1, 63–69.
| Crossref | GoogleScholarGoogle Scholar |
De Sousa PA,
King T,
Harkness L,
Young LE,
Walker SK, Wilmut I
(2001) Evaluation of gestational deficiencies in cloned sheep fetuses and placentae. Biology of Reproduction 65, 23–30.
| PubMed |
Eggan K,
Akutsu H,
Loring J,
Jackson-Grusby L,
Klemm M,
Rideout WM,
Yanagimachi R, Jaenisch R
(2001) Hybrid vigor, fetal overgrowth, and viability of mice derived by nuclear cloning and tetraploid embryo complementation. Proceedings of the National Academy of Sciences of the United States of America 98, 6209–6214.
| Crossref |
PubMed |
Enright BP,
Taneja M,
Schreiber D,
Riesen J,
Tian XC,
Fortune JE, Yang X
(2002) Reproductive characteristics of cloned heifers derived from adult somatic cells. Biology of Reproduction 66, 291–296.
| PubMed |
Galli C,
Lagutina I,
Crotti G,
Colleoni S,
Turini P,
Ponderato N,
Duchi R, Lazzari G
(2003) Pregnancy: a cloned horse born to its dam twin. Nature 424, 635.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Hakelien AM, Collas P
(2002) Novel approaches to transdifferentiation. Cloning and Stem Cells 4, 379–387.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Hill JR,
Burghardt RC,
Jones K,
Long CR,
Looney CR,
Shin T,
Spencer TE,
Thompson JA,
Winger QA, Westhusin ME
(2000) Evidence for placental abnormality as the major cause of mortality in first-trimester somatic cell cloned bovine fetuses. Biology of Reproduction 63, 1787–1794.
| PubMed |
Hill JR,
Roussel AJ,
Cibelli JB,
Edwards JF, Hooper RN , et al.
(1999) Clinical and pathologic features of cloned transgenic calves and fetuses (13 case studies). Theriogenology 51, 1451–1465.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Humpherys D,
Eggan K,
Akutsu H,
Hochedlinger K,
Rideout WM,
Biniszkiewicz D,
Yanagimachi R, Jaenisch R
(2001) Epigenetic instability in ES cells and cloned mice. Science 293, 95–97.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Jaenisch R,
Eggan K,
Humpherys D,
Rideout W, Hochedlinger K
(2002) Nuclear cloning, stem cells, and genomic reprogramming. Cloning and Stem Cells 4, 389–396.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Jaenisch R, Wilmut I
(2001) Developmental biology. Don’t clone humans! Science 291, 2552.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Keefer CL,
Baldassarre H,
Keyston R,
Wang B, Bhatia B , et al.
(2001) Generation of dwarf goat (Capra hircus) clones following nuclear transfer with transfected and nontransfected fetal fibroblasts and in vitro-matured oocytes. Biology of Reproduction 64, 849–856.
| PubMed |
Khosla S,
Dean W,
Reik W, Feil R
(2001) Culture of preimplantation embryos and its long-term effects on gene expression and phenotype. Human Reproduction Update 7, 419–427.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Lanza RP,
Cibelli JB,
Blackwell C,
Cristofalo VJ, Francis MK , et al.
(2000) Extension of cell life-span and telomere length in animals cloned from senescent somatic cells Science 288, 665–669.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Lanza RP,
Cibelli JB,
Faber D,
Sweeney RW,
Henderson B,
Nevala W,
West MD, Wettstein PJ
(2001) Cloned cattle can be healthy and normal. Science 294, 1893–1894.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Ogonuki N,
Inoue K,
Yamamoto Y,
Noguchi Y, Tanemura K , et al.
(2002) Early death of mice cloned from somatic cells. Nature Genetics 30, 253–254.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Onishi A,
Iwamoto M,
Akita T,
Mikawa S,
Takeda K,
Awata T,
Hanada H, Perry AC
(2000) Pig cloning by microinjection of fetal fibroblast nuclei. Science 289, 1188–1190.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Pace MM,
Augenstein ML,
Betthauser JM,
Childs LA, Eilertsen KJ , et al.
(2002) Ontogeny of cloned cattle to lactation. Biology of Reproduction 67, 334–339.
| PubMed |
Polejaeva IA,
Chen SH,
Vaught TD,
Page RL, Mullins J , et al.
(2000) Cloned pigs produced by nuclear transfer from adult somatic cells. Nature 407, 86–90.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Reggio BC,
James AN,
Green HL,
Gavin WG,
Behboodi E,
Echelard Y, Godke RA
(2001) Cloned transgenic offspring resulting from somatic cell nuclear transfer in the goat: oocytes derived from both follicle-stimulating hormone-stimulated and nonstimulated abattoir-derived ovaries. Biology of Reproduction 65, 1528–1533.
| PubMed |
Rideout WM,
Eggan K, Jaenisch R
(2001) Nuclear cloning and epigenetic reprogramming of the genome. Science 293, 1093–1098.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Schnieke AE,
Kind AJ,
Ritchie WA,
Mycock K,
Scott AR,
Ritchie M,
Wilmut I,
Colman A, Campbell KH
(1997) Human factor IX transgenic sheep produced by transfer of nuclei from transfected fetal fibroblasts. Science 278, 2130–2133.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Shiels PG,
Kind AJ,
Campbell KH,
Waddington D,
Wilmut I,
Colman A, Schnieke AE
(1999) Analysis of telomere lengths in cloned sheep. Nature 399, 316–317.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Shin T,
Kraemer D,
Pryor J,
Liu L,
Rugila J,
Howe L,
Buck S,
Murphy K,
Lyons L, Westhusin M
(2002) A cat cloned by nuclear transplantation. Nature 415, 859.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Stice SL,
Strelchenko NS,
Keefer CL, Matthews L
(1996) Pluripotent bovine embryonic cell lines direct embryonic development following nuclear transfer. Biology of Reproduction 54, 100–110.
| PubMed |
Tamashiro KL,
Wakayama T,
Blanchard RJ,
Blanchard DC, Yanagimachi R
(2000) Postnatal growth and behavioral development of mice cloned from adult cumulus cells. Biology of Reproduction 63, 328–334.
| PubMed |
Tian XC,
Xu J, Yang X
(2000) Normal telomere lengths found in cloned cattle. Nature Genetics 26, 272–273.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Wakayama T,
Perry AC,
Zuccotti M,
Johnson KR, Yanagimachi R
(1998) Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei. Nature 394, 369–374.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Wells DN,
Misica PM,
Forsyth JT,
Berg MC,
Lange JM,
Tervit HR, Vivanco WH
(1999) The use of adult somatic cell nuclear transfer to preserve the last surviving cow of the Enderby Island cattle breed. Theriogenology 51, 217.
| Crossref | GoogleScholarGoogle Scholar |
Wells DN,
Misica PM, Tervit HR
(1999) Production of cloned calves following nuclear transfer with cultured adult mural granulosa cells. Biology of Reproduction 60, 996–1005.
| PubMed |
Wilmut I,
Beaujean N,
De Sousa PA,
Dinnyes A,
King TJ,
Paterson LA,
Wells DN, Young LE
(2002) Somatic cell nuclear transfer. Nature 419, 583–586.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Wilmut I,
Schnieke AE,
McWhir J,
Kind KL, Campbell KHS
(1997) Viable offspring derived from fetal and adult mammalian cells. Nature 385, 810–813.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Winger QA,
Hill JR,
Shin T,
Watson AJ,
Kraemer DC, Westhusin ME
(2000) Genetic reprogramming of lactate dehydrogenase, citrate synthase, and phosphofructokinase mRNA in bovine nuclear transfer embryos produced using bovine fibroblast cell nuclei. Molecular Reproduction and Development 56, 458–464.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Young LE, Fairburn HR
(2000) Improving the safety of embryo technologies: possible role of genomic imprinting. Theriogenology 53, 627–648.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Young LE,
Fernandes K,
McEvoy TG,
Butterwith SC,
Gutierrez CG,
Carolan C,
Broadbent PJ,
Robinson JJ,
Wilmut I, Sinclair KD
(2001) Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture. Nature Genetics 27, 153–154.
| Crossref | GoogleScholarGoogle Scholar | PubMed |