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Scientists created mice with mammoth genes: what happened

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Scientists from the American biotechnology company Colossal Biosciences have altered several genes in mice to make them more similar to mammoths, but the company is far from its goal of fully "reviving" woolly mammoths by 2028. This was reported by The Guardian, as noted by UNN.

Details

There are approximately 1.5 million genetic differences between woolly mammoths and Asian elephants. Colossal Biosciences, a company aiming to resurrect extinct species through genetic engineering, has created mice with "mammoth" fur, each having up to five genetic changes.

It is noted that the fur on these mice is long, curly, and blonde. Thus, it truly resembles the fur of mammoths, the remains of which have survived to this day. However, it is unclear whether making the same genetic changes to Asian elephants, which have far fewer hairs on their skin, will yield similar results.

"The work done on these mice does not mean that there is a ready solution for returning the mammoth phenotype. We also need to figure out how to make the fur grow more," says team member Love Dalén from Stockholm University in Sweden, who is part of the scientific advisory board of Colossal.

Creating Asian elephants with such genetic changes will also be much harder than doing so in mice.

"Engineering mutations in mice is a well-established process and is not particularly complicated," noted Duško Ilić from King's College London.

So how did Colossal create its "mammoth" mice? Researchers began by searching for known mutations in mice that make their fur resemble that of a mammoth.

Most of these genes were selected based on previous observations of fur phenotypes in mice

- they write in a paper published today that has not been peer-reviewed.

They identified eight genes that affect the pattern (curliness), color, and length of fur. According to scientists, one of these eight genes is present in mammoths.

In the mammoth genome, the team also discovered a small mutation believed to affect hair structure, as well as another non-functional gene involved in fat metabolism.

The company then attempted to alter these genes in mice. For example, in one experiment, they tried to knock out five of these genes in fertilized eggs using CRISPR gene editing. Out of 134 eggs, 11 pups were born, and one of them had both copies of the five genes turned off.

In another study, researchers used a form of CRISPR called "base editing" to knock out several genes in mouse embryonic stem cells. They combined this with another technique called homologous recombination to make the precise mutation found in the mammoth genome. Making precise changes is much more complex than knocking out genes, but the recombination method works well only in mice.

The team then sequenced the cells to identify those with the desired changes and introduced them into mouse embryos to create chimeric mice. Out of 90 introduced embryos, seven mice were born with four planned changes.

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It can be said that these experiments were successful in terms of producing some mice with the desired physical changes in their fur, but only one of the genetic changes exactly corresponds to what is seen in the mammoth genome. According to the scientist, much work remains to be done to achieve the stated goal of creating a "cold-resistant elephant with all the key biological traits of the woolly mammoth" - and since the gestation period for elephants lasts about two years, scientists are running out of time to meet their deadline - 2028.

Juan Antonio Rodríguez from the University of Copenhagen (Denmark) says, "An elephant with fur will not be a mammoth in the way we think of it." He notes that many of the 1.5 million differences between the genomes of mammoths and Asian elephants may not matter, but we do not know for sure which of them are significant.

Rodríguez and Lynch oppose the resurrection of the mammoth. Lynch provides a long list of reasons why he believes it is a bad idea, from the fact that there is no longer a habitat for mammoths to the ethical aspects of attempting to genetically modify elephants – for example, even in humans, egg retrieval for IVF remains a risky and painful procedure.

"Mammoths are extinct, and they cannot be 'unextinct' or revived," says Lynch. "All they can do is make an elephant look like a mammoth."

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