Megan and Morag, two

domestic sheep Sheep or domestic sheep (''Ovis aries'') are domesticated, ruminant mammals typically kept as livestock. Although the term ''sheep'' can apply to other species in the genus '' Ovis'', in everyday usage it almost always refers to domesticated ...

, were the first mammals to have been successfully

cloned Cloning is the process of producing individual organisms with identical or virtually identical DNA, either by natural or artificial means. In nature, some organisms produce clones through asexual reproduction. In the field of biotechnology, ...

from differentiated cells. They are not to be confused with

Dolly the sheep Dolly (5 July 1996 – 14 February 2003) was a female Finnish Dorset sheep and the first mammal 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 ...

which was the first animal to be successfully cloned from an adult somatic cell or

Polly the sheep Polly and Molly (born 1997), two ewes, were the first mammals to have been successfully cloned from an adult somatic cell and to be transgenic animals at the same time. This is not to be confused with Dolly the Sheep, the first animal to be succe ...

which was the first cloned and transgenic animal. Megan and Morag, like Dolly and Polly, were cloned at the

Roslin Institute 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. It is best known for creat ...

Edinburgh Edinburgh ( ; gd, Dùn Èideann ) is the capital city of Scotland and one of its 32 council areas. Historically part of the county of Midlothian (interchangeably Edinburghshire before 1921), it is located in Lothian on the southern shore of t ...

Scotland Scotland (, ) is a Countries of the United Kingdom, country that is part of the United Kingdom. Covering the northern third of the island of Great Britain, mainland Scotland has a Anglo-Scottish border, border with England to the southeast ...

in 1995.

Background

The team at the

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 Microinjection is the use of a glass micropipette to inject a liquid substance at a microscopic or borderline macroscopic level. The target is often a living cell but may also include intercellular space. Microinjection is a simple mechanical pro ...

. 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 cell Embryonic stem cells (ESCs) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre- implantation embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist ...

s. 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 Nuclear transfer is a form of cloning. The step involves removing the DNA from an oocyte (unfertilised egg), and injecting the nucleus which contains the DNA to be cloned. In rare instances, the newly constructed cell will divide normally, rep ...

. 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

possible. The birth of Megan and Morag, a year before Dolly, with their huge beneficial potential, made relatively few headlines. , Megan was still alive and was the oldest cloned animal at the time.

References

{{Reflist 1995 animal births Cloning Cloned sheep Vertebrate developmental biology Cell biology Stem cells Biotechnology Individual animals in the United Kingdom