Stuffed animal-like mice: a first step toward de-extincting mammoths?

One of the news stories of the month is the publication in the media of a story about plush-like mice with fluffy, golden fur, with an enticing headline about the resurrection of mammoth genes. These mice were created by a privately held biotechnology company, Colossal, which aims to de-extinct species, has set its sights on the mammoth. Aside from the obvious appeal to potential investors, why the mammoth and not any other species? According to the company, They intend to contribute to repopulating the Arctic tundra with mammoths., and solve the problem of the release of CO₂ by permafrost, which would contribute to combating climate change.

This would be a great milestone, but it would need to be cooled down through predictive ecological studies, since mammoths became extinct due to environmental changes and a drastic decline in animal numbers, which reduced the genetic variability of the species to unsustainable limits, with an increase in deleterious diseases due to inbreeding. The last specimens lived 4,000 years ago on the Arctic island of Wrangel. Reintroduce herds of mammoths (assuming this can be done) into ecosystems that have been around for thousands of years without having catastrophic effects on the species that currently inhabit them.

Can a species be de-extincted?

However, there are other reasons why this company is pursuing a seemingly impossible goal. The mammoth, Mammuthus primigenius, is genetically close to the Asian elephant (Elephas maximus), a proboscidean belonging to a different genus from the African elephant species (genus Loxodonta). The company's goal is to obtain an Asian elephant that closely resembles a mammoth. Therefore, they would not intend to resurrect the mammoth, but mammothize the elephant to obtain an animal with genetic variants that mimic the characteristics of a mammoth, including long, curly hair, fat accumulation, and outward-curving tusks.

The ultimate goal is extremely complicated and difficult. So far, they have been able to find very well-preserved biological remains of mammoths, sequencing their genomes, and also Asian elephants for comparison. They have identified specific genetic variants of the prehistoric animal that would allow it to survive and feed in extremely cold habitats. However, regarding the cultivation of elephant cells and the reintroduction of the identified mammoth variants, methodologically very complex processes, they have preferred to cut corners and work with another animal, the mouse.

It is not feasible to use elephants.

It must be said that our knowledge of the mouse genome, genes, and development is much more thorough than that of the elephant: we understand the mouse's physiological system very well, we know how to generate embryos, and we have mastered genetic modification techniques. Furthermore, reproductively, mice have a 21-day pregnancy, with multiple litters, and are easy to care for and reproduce. In contrast, elephants have a 2-year pregnancy and a single fetus, and are a very delicate species to care for and reproduce in captivity. Genetic modification techniques require many embryos to be introduced into surrogate mothers for implantation, and it is evident that It is not feasible to use Asian elephants to produce hundreds of embryos to find the one in which all the modifications converge.. At least with current techniques.

Furthermore, there are some 500,000 differences between the mammoth and elephant genomes, although researchers estimate that only a hundred would be enough to introduce some of their characteristics. So the researchers have taken a shortcut and wanted to see if they can introduce some genetic variants into mice—which have real grayish fur—to produce rodents with something fluffy and golden, just like the one that would protect mammoths from the cold.

Mice with mammoth skin

To do this, and as they have communicated in an article not yet reviewed by other scientists, They have chosen 10 genes from the mouse genome to modify themFor the vast majority of the selected genes, it was previously known that their mutation or modification caused the desired, specific effect on mouse hair. In fact, only three of the modified genes were "inspired" by the genetic differences between mammoths and Asian elephants.

The researchers used up to four different genetic modification and editing strategies in mouse embryos and embryonic stem cells, making simultaneous modifications (a technical advance that can be used in other contexts) and They obtained mice with up to seven genetic modifications, including mutations in the Mc1r gene, which gives it a slightly reddish-gold color; mutations in the eight other genes that produce longer, thicker, curlier, and angled growth; and a variant in the Fabp2 gene, which is thought to contribute to the accumulation of more subcutaneous fat, which is useful for protection against the cold.

Modified mice look so stuffedBut the researchers haven't resurrected any mammoth genes, by any means! What they've done, successfully, is demonstrate that certain genes control these characteristics of mammalian hair, and it's very likely that if they're ever introduced into elephant embryos, assuming the fetus ever survives, at least some of them will make it possible to have a hairy elephant. But there's still a long way to go from there to having a mammoth. You have to be careful, in science.