Megan and Morag (cloned sheep)
Encyclopedia
Megan and Morag, two domestic sheep
, were the first mammals to have been successfully cloned
from differentiated cells. They are not to be confused with Dolly the Sheep
which was the first animal to be successfully cloned from an adult somatic cell or Polly the sheep which was the first cloned and transgenic animal. Megan and Morag, like Dolly the Sheep
and Polly the sheep were cloned at the Roslin Institute in Edinburgh
, Scotland
in 1995.
. In Microinjection
, DNA is injected into the pronucleii 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 no headlines. , Megan was still alive and was the oldest cloned animal at the time.
Domestic sheep
Sheep are quadrupedal, ruminant mammals typically kept as livestock. Like all ruminants, sheep are members of the order Artiodactyla, the even-toed ungulates. Although the name "sheep" applies to many species in the genus Ovis, in everyday usage it almost always refers to Ovis aries...
, were the first mammals to have been successfully cloned
Cloning
Cloning in biology is the process of producing similar populations of genetically identical individuals that occurs in nature when organisms such as bacteria, insects or plants reproduce asexually. Cloning in biotechnology refers to processes used to create copies of DNA fragments , cells , or...
from differentiated cells. They are not to be confused with Dolly the Sheep
Dolly the Sheep
Dolly was a female domestic sheep, and the first mammal to be cloned from an adult somatic cell, using the process of nuclear transfer. She was cloned by Ian Wilmut, Keith Campbell and colleagues at the Roslin Institute near Edinburgh in Scotland...
which was the first animal to be successfully cloned from an adult somatic cell or Polly the sheep which was the first cloned and transgenic animal. Megan and Morag, like Dolly the Sheep
Dolly the Sheep
Dolly was a female domestic sheep, and the first mammal to be cloned from an adult somatic cell, using the process of nuclear transfer. She was cloned by Ian Wilmut, Keith Campbell and colleagues at the Roslin Institute near Edinburgh in Scotland...
and Polly the sheep were cloned at the Roslin Institute in Edinburgh
Edinburgh
Edinburgh is the capital city of Scotland, the second largest city in Scotland, and the eighth most populous in the United Kingdom. The City of Edinburgh Council governs one of Scotland's 32 local government council areas. The council area includes urban Edinburgh and a rural area...
, Scotland
Scotland
Scotland is a country that is part of the United Kingdom. Occupying the northern third of the island of Great Britain, it shares a border with England to the south and is bounded by the North Sea to the east, the Atlantic Ocean to the north and west, and the North Channel and Irish Sea to the...
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 – MicroinjectionMicroinjection
Microinjection refers to the process of using a glass micropipette to insert substances at a microscopic or borderline macroscopic level into a single living cell. It is a simple mechanical process in which a needle roughly 0.5 to 5 micrometers in diameter penetrates the cell membrane and/or the...
. In Microinjection
Microinjection
Microinjection refers to the process of using a glass micropipette to insert substances at a microscopic or borderline macroscopic level into a single living cell. It is a simple mechanical process in which a needle roughly 0.5 to 5 micrometers in diameter penetrates the cell membrane and/or the...
, DNA is injected into the pronucleii 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
Microinjection
Microinjection refers to the process of using a glass micropipette to insert substances at a microscopic or borderline macroscopic level into a single living cell. It is a simple mechanical process in which a needle roughly 0.5 to 5 micrometers in diameter penetrates the cell membrane and/or the...
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
Nuclear transfer
Nuclear Transfer is a form of cloning. The steps involve removing the DNA from an oocyte , and injecting the nucleus which contains the DNA to be cloned. In rare instances, the newly constructed cell will divide normally, replicating the new DNA while remaining in a pluripotent state...
. The team at the Roslin Institute tried to make immortalized and undifferentiated Embryonic stem cell
Embryonic stem cell
Embryonic stem cells are pluripotent stem cells derived from the inner cell mass of the blastocyst, an early-stage embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells...
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
Nuclear transfer
Nuclear Transfer is a form of cloning. The steps involve removing the DNA from an oocyte , and injecting the nucleus which contains the DNA to be cloned. In rare instances, the newly constructed cell will divide normally, replicating the new DNA while remaining in a pluripotent state...
, 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
Nuclear transfer
Nuclear Transfer is a form of cloning. The steps involve removing the DNA from an oocyte , and injecting the nucleus which contains the DNA to be cloned. In rare instances, the newly constructed cell will divide normally, replicating the new DNA while remaining in a pluripotent state...
from cells which have been cultured in vitro. They signified the technical breakthrough that made Dolly the sheep
Dolly the Sheep
Dolly was a female domestic sheep, and the first mammal to be cloned from an adult somatic cell, using the process of nuclear transfer. She was cloned by Ian Wilmut, Keith Campbell and colleagues at the Roslin Institute near Edinburgh in Scotland...
possible. The birth of Megan and Morag, a year before Dolly, with their huge beneficial potential, made no headlines. , Megan was still alive and was the oldest cloned animal at the time.