A company that has raised hundreds of millions of dollars in an effort to ‘de-extinct’ woolly mammoths and other animals has claimed a breakthrough in its quest: the creation of hairier mice.
The gene-edited ‘woolly mice’ harbour a mix of mutations modelled on those of woolly mammoths (Mammuthus primigenius), as well as changes known to alter hair growth in mice, Colossal Biosciences announced in a 4 March press release and accompanying preprint1.
Colossal, which is based in Dallas, Texas, and is worth more than US$10 billion according to its latest valuation, says the woolly mouse represents an important step towards its goal of engineering Asian elephants — the mammoth’s closest living relative — with genetic changes for key mammoth traits. “The Colossal Woolly Mouse marks a watershed moment in our de-extinction mission,” said Ben Lamm, Colossal’s co-founder and chief executive, in the press release.
But some specialists in mammoth genetics and genome editing question whether the mice represent a significant advance in either area, let alone a milestone on the way to bringing back woolly mammoths, which last roamed Earth some 4,000 years ago.
“It’s far away from making a mammoth or a ‘mammoth mouse’,” says Stephan Riesenberg, a genome engineer at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. “It’s just a mouse that has some special genes.”
Shaggy-hair gene
As part of its effort to engineer mammoth-like elephants, Colossal and its collaborators are working to find gene variants that contributed to key mammoth traits, such as shaggy hair, cold tolerance and extra fat stores. To do this, they compare genomes extracted from the remains of dozens of mammoths and from other living and extinct relatives of the creatures, in search of protein-altering changes that evolved on the mammoth lineage.
The woolly mice tended to have tawny-toned shaggy hair.Credit: Colossal Biosciences
To test the accuracy of these comparisons, a team led by Beth Shapiro, Colossal’s chief scientist, used gene editing to create mice with mutations similar — but in most cases not identical — to those found in mammoths. Shapiro says the group also tested several gene mutations known to affect the hair of mice but not found in mammoths.
The researchers used different gene-editing tools to create mice with up to eight genetic alterations spread across seven genes. These mice tended to have long, shaggy hair that, owing to a mutation known to affect hair colour in mice, humans and mammoths, was tawny-toned instead of the usual dark grey. “Adorability was one of the unintended consequences that we did not expect,” Lamm says. Mice with a mammoth-inspired change to a gene involved in fat metabolism were no heavier than were mice with unedited genes.
The mice are only a few months old, and the researchers have not had much time to investigate how the mutations might affect their long-term health, including their fertility and propensity to develop cancers. The researchers plan to test whether the mice are any better at handling the cold than other mice, and to study their hair development.
Lamm says the company has no plans to breed or sell the mice commercially. But for about $3,500, scientists can purchase a shaggy-haired mouse strain known as ‘wooly’ from the Jackson Laboratory in Bar Harbor, Maine, which first bred the mice more than two decades ago. Researchers later showed that the strain carries a mutation in a gene called Fam83g — one of the genes inactivated in Colossal’s woolly mice.
Woolly mammoths share many genes with Asian elephants.Credit: Darryl Brooks/Alamy
Showing that changes found in mammoth genomes can affect mouse biology is a useful proof of principle, says Alfred Roca, a population geneticist at the University of Illinois Urbana–Champaign, who sees the experiments as a step towards engineering elephants with mammoth traits. “It’s a very nice visualization of where you want to end up in the mammoth.”
