With curly whiskers and wavy, light-colored fur that grows three times longer than that of a typical lab mouse, the genetically engineered rodent exhibits several traits reminiscent of the woolly mammoth, according to Colossal Biosciences. The private Dallas-based company is leading efforts to revive the mammoth and other extinct species.
Colossal stated that the woolly mouse will help its scientists explore the connection between specific DNA sequences and the physical characteristics that allowed the mammoth—which disappeared around 4,000 years ago—to thrive in icy environments.
“This is a significant step in confirming our approach to bringing back traits lost to extinction, which we aim to restore,” said Dr. Beth Shapiro, Colossal’s chief science officer, in a press release on Tuesday. Shapiro is currently on a leave of absence from her position as a professor of ecology and evolutionary biology at the University of California, Santa Cruz.
How to make a woolly mouse
To develop the woolly mouse, Colossal stated that it identified genetic variations where mammoths differed from their closest living relative, the Asian elephant.
The company’s researchers then isolated 10 specific variants associated with hair length, thickness, texture, color, and body fat—matching them to equivalent, well-documented DNA variations found in lab mice.
For instance, researchers focused on a gene called FGF5 (fibroblast growth factor 5), which regulates the hair growth cycle, resulting in longer, shaggier fur. Additionally, they modified the function of three other genes involved in hair follicle development and structure to produce a woolly hair texture, wavy coats, and curled whiskers, according to the company’s press release.
The researchers also targeted the MC1R gene (melanocortin 1 receptor), which controls melanin production, to create mice with golden fur instead of their typical dark coloring. Additionally, they modified a genetic variant linked to body weight changes.
In total, the team made eight genetic edits at once, utilizing three advanced techniques to modify seven genes in the mice.
Colossal released a preprint scientific paper detailing the research, though it has not yet undergone peer review.
“The ability to edit multiple genes simultaneously in mice and successfully achieve the expected woolly appearance is a significant milestone,” said Love Dalén, a professor of evolutionary genomics at Stockholm University. Dalén, who serves as an advisor to Colossal, also coauthored the study.
“This serves as proof of concept that Colossal possesses the expertise to carry out this type of genetic editing, including introducing mammoth gene variants into another species.”
Just ‘cute, hairy-looking mice’?
The research described in the unpublished paper was technically impressive, with precise and efficient genetic modifications, according to Robin Lovell-Badge, head of the Stem Cell Biology and Developmental Genetics Laboratory at The Francis Crick Institute in London.
“My main concern with the paper is that it doesn’t address whether the genetically modified mice exhibit cold tolerance—by introducing traits seen in mammoths—which was the stated reason for conducting this study,” Lovell-Badge said via email.
“As it stands, we have some fluffy, unusual-looking mice, but no real insight into their physiology, behavior, or other biological functions. This doesn’t necessarily bring us closer to determining whether these modifications could eventually provide elephants with useful mammoth-like traits, and it contributes little to our understanding of biology.”
Colossal has raised $435 million since its founding in 2021 by entrepreneur Ben Lamm and Harvard University geneticist George Church.
The company aims to bring back the mammoth, dodo, and Tasmanian tiger (thylacine) by editing the genomes of each species’ closest living relative, creating hybrid animals that would closely resemble their extinct ancestors. Ultimately, Colossal hopes to reintroduce these animals into their natural habitats.
For mammoths, the company proposes that having mammoth-like creatures roam the Arctic would compact the snow and grass, reducing the insulation of the ground and slowing the thawing of permafrost, which helps prevent the release of carbon from this vulnerable ecosystem. Colossal has previously stated that it expects to introduce the first woolly mammoth calves by 2028.
Critics argue that the substantial investment in the project could be better allocated to other causes. They warn that breeding and raising the hybrid animals might endanger the living animals used as surrogates.
“While we have a deep understanding of mouse genetics, we know much less about mammoths and elephants. It’s still unclear which genomic elements are key to adapting an elephant for Arctic life,” said Tori Herridge, Senior Lecturer at the University of Sheffield’s School of Biosciences, in a statement from the Science Media Centre. “Genes linked to fur and fat in well-researched animals like mice are clear targets, but the real challenge is in the details.”
“Without making all the necessary genetic edits, you’ll only create a rough approximation of an extinct species, based on an incomplete view of what it should look like. You won’t truly ‘bring back’ a mammoth,” she added.
Lab mice are often genetically modified to express specific traits, including human ones, to aid in research on diseases and drug development.
Rob Taft, a principal scientist at The Jackson Laboratory, a biomedical research institution known for pioneering humanized lab mice, said in an email that the woolly mouse is an “innovative extension of the mouse as a model system and a novel approach to studying the physiology of extinct animals.”
His main concern was how Colossal would apply this research to elephants.
“Working with mice or even cattle is relatively straightforward,” Taft explained. “We have a solid understanding of reproduction in these species, and assisted reproductive technologies are well-established and commonly used. However, there’s still much to learn about elephant reproduction, and assisted reproductive technologies aren’t as advanced for elephants.”