Megan and Morag

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Megan and Morag, two domestic sheep, were the first mammals to have been successfully cloned from differentiated cells. [1] They are not to be confused with Dolly the sheep which was the first animal to be successfully cloned from an adult somatic cell [2] or Polly the sheep which was the first cloned and transgenic animal. [3] Megan and Morag, like Dolly and Polly, were cloned at the Roslin Institute in Edinburgh, Scotland in 1995.

Background

The team at the Roslin Institute were seeking a way to modify the genetic constitution of sheep and cattle more effectively than the hit and miss method that was the only method and had sort of aids available at the time – microinjection. In microinjection, DNA is injected into the pronuclei of fertilized oocytes. However, only a small proportion of the animals will integrate the injected DNA into their genome and in the rare cases that they do integrate this new genetic information, the pattern of expression of the injected piece of DNA's gene, due to the random integration, is very variable.

The team choose to combine two approaches – microinjection and embryonic stem cells. In order to achieve this they decided to try to transfer the nucleus from one cell to another and stimulate this new cell to grow and become an animal, a process known as nuclear transfer. The team at the Roslin Institute tried to make immortalized and undifferentiated embryonic stem cell lines in sheep, but failed. As a result, they decided to work with cultured blastocyst cells. The nuclear material of these blastocyst cells would be transferred into an unfertilized sheep egg cell, an oocyte where the nucleus had been removed. To optimize the chances of successful nuclear transfer, they put the cultured cells into a state of quiescence, which was a similar state to that of the unfertilized egg cell.

Nuclear transfer was done, using electrical stimuli both to fuse the cultured cell with the enucleated egg and to kick start embryonic development. From 244 nuclear transfers, 34 developed to a stage where they could be placed in the uteri of surrogate mothers. In the summer of 1995, five lambs were born, of which two – Megan and Morag – survived to become healthy fertile adults. These were the first mammals cloned from differentiated cells. They were born with the names 5LL2 and 5LL5 in June 1995.

The production of Megan and Morag demonstrated that viable sheep can be produced by nuclear transfer from cells which have been cultured in vitro. They signified the technical breakthrough that made Dolly the sheep possible. The birth of Megan and Morag, a year before Dolly, with their huge beneficial potential, made relatively few headlines. [4] As of 2005, Megan was still alive and was the oldest cloned animal at the time. [5]

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<span class="mw-page-title-main">Cloning</span> Process of producing individual organisms with identical genomes

Cloning is the process of producing individual organisms with identical genomes, either by natural or artificial means. In nature, some organisms produce clones through asexual reproduction; this reproduction of an organism by itself without a mate is known as parthenogenesis. In the field of biotechnology, cloning is the process of creating cloned organisms of cells and of DNA fragments.

<span class="mw-page-title-main">Dolly (sheep)</span> First cloned mammal (1996–2003)

Dolly was a female Finn-Dorset sheep and the first mammal that was cloned from an adult somatic cell. She was cloned by associates of the Roslin Institute in Scotland, using the process of nuclear transfer from a cell taken from a mammary gland. Her cloning proved that a cloned organism could be produced from a mature cell from a specific body part. Contrary to popular belief, she was not the first animal to be cloned.

<span class="mw-page-title-main">Human cloning</span> Creation of a genetically identical copy of a human

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<span class="mw-page-title-main">Somatic cell nuclear transfer</span> Method of creating a cloned embryo by replacing the egg nucleus with a body cell nucleus

In genetics and developmental biology, somatic cell nuclear transfer (SCNT) is a laboratory strategy for creating a viable embryo from a body cell and an egg cell. The technique consists of taking an denucleated oocyte and implanting a donor nucleus from a somatic (body) cell. It is used in both therapeutic and reproductive cloning. In 1996, Dolly the sheep became famous for being the first successful case of the reproductive cloning of a mammal. In January 2018, a team of scientists in Shanghai announced the successful cloning of two female crab-eating macaques from foetal nuclei.

<span class="mw-page-title-main">Embryonic stem cell</span> Pluripotent stem cell of the inner cell mass of the blastocyst

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Sir Ian Wilmut, OBE FRS FMedSci FRSE is an English embryologist and Chair of the Scottish Centre for Regenerative Medicine at the University of Edinburgh. He is best known as the leader of the research group that in 1996 first cloned a mammal from an adult somatic cell, a Finnish Dorset lamb named Dolly. He was appointed OBE in 1999 for services to embryo development and knighted in the 2008 New Year Honours. He together with Keith Campbell and Shinya Yamanaka jointly received the 2008 Shaw Prize for Medicine and Life Sciences "for their works on the cell differentiation in mammals."

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The Roslin Institute is an animal sciences research institute at Easter Bush, Midlothian, Scotland, part of the University of Edinburgh, and is funded by the Biotechnology and Biological Sciences Research Council.

<i>In re Roslin Institute</i> (Edinburgh) 2014 decision of the United States Court of Appeals for the Federal Circuit

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References

  1. Campbell, K. H. S.; McWhir, J.; Ritchie, W. A.; Wilmut, I. (7 March 1996). "Sheep cloned by nuclear transfer from a cultured cell line". Nature. 380 (6569): 64–66. Bibcode:1996Natur.380...64C. doi:10.1038/380064a0. PMID   8598906. S2CID   3529638.
  2. Wilmut, I.; Schnieke, A. E.; McWhir, J.; Kind, A. J.; Campbell, K. H. S. (27 February 1997). "Viable offspring derived from fetal and adult mammalian cells". Nature. 385 (6619): 810–813. Bibcode:1997Natur.385..810W. doi:10.1038/385810a0. PMID   9039911.
  3. McCreath, K. J.; Howcroft, J.; Campbell, K. H. S.; Colman, A.; Schnieke, A. E.; Kind, A. J. (29 June 2000). "Production of gene-targeted sheep by nuclear transfer from cultured somatic cells". Nature. 405 (6790): 1066–1069. Bibcode:2000Natur.405.1066M. doi:10.1038/35016604. PMID   10890449. S2CID   4419356.
  4. "Archived copy" (PDF). Archived from the original (PDF) on 2016-12-24. Retrieved 2016-11-04.{{cite web}}: CS1 maint: archived copy as title (link)
  5. "Megan turns 10". Melbourne: theage.com. 2005-06-17. Retrieved 2007-07-02.