Genetically engineered mouse with woolly fur is a step toward resurrecting extinct mammoth, company says

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It’s tiny, but this lab mouse could have a mammoth impact.

With curly whiskers and wavy, light hair that grows three times longer than that of an ordinary lab mouse, the genetically modified rodent embodies several woolly mammoth-like traits, according to Colossal Biosciences. The private Dallas company is behind efforts to resurrect the mammoth and other extinct animals.

Colossal said its woolly mouse would enable its scientists to test hypotheses about the link between specific DNA sequences and physical traits that enabled the mammoth, which went extinct around 4,000 years ago, to adapt to life in cold climates.

“It is an important step toward validating our approach to resurrecting traits that have been lost to extinction and that our goal is to restore,” said Dr. Beth Shapiro, chief science officer at Colossal, in a news release Tuesday. Shapiro is currently on a leave of absence from her role as professor of ecology and evolutionary biology at the University of California, Santa Cruz.

How to make a woolly mouse

To create the woolly mouse, Colossal said it had identified genetic variants in which mammoths differed from their closest living relative: the Asian elephant.

The company’s scientists then pinpointed 10 variants related to hair length, thickness, texture, color and body fat that corresponded to similar, known DNA variants in a lab mouse.

For example, scientists targeted a gene known as FGF5 (fibroblast growth factor 5), which targets the cycle of hair growth, creating longer, shaggy hair. They also altered the function of three genes related to hair follicle development and structure to create woolly hair texture, wavy coats and curled whiskers, the company said in a news release.

Other target genes included MC1R (melanocortin 1 receptor), which regulates melanin production, in order to produce mice with golden hair rather than the usual dark fur and a variant associated with changes in body weight.

In total, the team made eight edits simultaneously, using three cutting-edge techniques, to seven mice genes.

Colossal shared an unpublished, or preprint, scientific paper describing the research, which has not undergone peer review.

“I think that the ability to edit multiple genes at the same time in mice, and to do so and obtain the expected woolly appearance, is a very important step,” said Love Dalén, a professor of evolutionary genomics at Stockholm University. Dalén is an advisor to Colossal and was a coauthor on the paper.

“It is a proof-of-principle that Colossal has the know-how to do this kind of gene editing, including to insert mammoth gene variants into a different species.”

Just ‘cute, hairy-looking mice’?

The research outlined in the unpublished paper was technically impressive and the genetic changes precise and efficient, said Robin Lovell-Badge, head of the Stem Cell Biology and Developmental Genetics Laboratory at The Francis Crick Institute in London.

“My biggest problem with the paper is that there is nothing addressing whether the modified mice are cold-tolerant — through introducing traits that are apparent in mammoths — which is the justification given for carrying out the work,” Lovell-Badge said via email.

“As it is, we have some cute looking hairy mice, with no understanding of their physiology, behaviour, etc. It doesn’t get them any closer to know if they would eventually be able to give an elephant useful mammoth-like traits and we have learned little biology.”

Colossal has raised $435 million since it was founded in 2021 by entrepreneur Ben Lamm and Harvard University geneticist George Church.

The company plans to recreate the mammoth, dodo, and Tasmanian tiger, or thylacine, by editing the genome of each species’ closest living relative to make a hybrid animal that would be visually indistinguishable from its extinct forerunner. Ultimately, the company wants to restore the fauna to their natural habitat.

In the case of mammoths, the company argues that having mammoth-like creatures lumbering through the Arctic would compress the snow and grass that insulates the ground, slowing the rate of permafrost thaw and the release of carbon contained in this fragile ecosystem. Colossal has previously said it’s on track to introduce the first woolly mammoth calves in 2028.

Skeptics argue that the huge sums of money invested in the project could be better spent elsewhere. Raising and breeding the hybrid animals, they say, could imperil living animals used as surrogates.

“While we know a lot about mouse genetics, we know much less about mammoths and elephants. It isn’t yet known which sections of the genome are vital for achieving the characters (needed) to make an elephant fit for life in the Arctic circle,” said Tori Herridge, Senior Lecturer, School of Biosciences, University of Sheffield, in a statement shared by the Science Media Centre. “Genes that are linked to fur and fat in well-studied animals like mice are obvious targets, but the devil is in the detail.”

“Unless you decide to make EVERY edit necessary … in the genome, you are only ever going to create a crude approximation of any extinct creature, based on an incomplete idea of what it should look like. You are never going to ‘bring back’ a mammoth,” she added.

Lab mice are commonly genetically engineered to have certain traits, including human ones, in order to conduct research on disease and drug development.

Rob Taft, a principal scientist at The Jackson Laboratory, a biomedical research institution that helped pioneer humanized lab mice, said via email that the woolly mouse was an “innovative extension of the use of the mouse as a model system and an innovative approach to understanding the physiology of animals that are now extinct.”

His biggest question was how Colossal would translate this research back to elephants.

“Working with mice or even cattle is relatively easy,” Taft said. “We know a lot about reproduction in these species and assisted reproductive technologies are well developed and used routinely in these species but there’s a lot about elephant reproduction that is not known and assisted reproductive technologies are not well developed for use in elephants.”

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