ON THE WAY TO HUMAN-MOUSE: why are scientists creating chimera animals
Sergiy Cheremisin. Exodus of the leader, 2023 / Facebook, «Sil-Sol»
Ancient Greek myths have brought us the image of a strange creature with the head of a lion, the body of a goat, and the tail of a snake — the Chimera. Homer claimed that this animal was purposefully raised by the Lycian king Amisodarus. The word «chimeric» is commonly used to denote fiction, some unfulfilled idea. However, modern scientists who have followed in Amisodarus’ footsteps have learned how to create chimeric animals. The scientific journal Nature tells us why they do it.
CHIMERAS HELP US UNDERSTAND HOW THE BRAIN DEVELOPS
Scientists have been creating hybrid or chimeric animals for years and have had some success. Rodents are the main laboratory animals, accounting for the largest share of such experiments.
So there were mice with rat organs, for example, with rat pancreas, as well as mice in whose brains rat and even human neurons had been planted. New research from Columbia University (USA, New York) has helped to understand whether rat neurons are able to fully integrate into the circuits of the mouse brain and become a full-fledged component of the behavioral control system of the host animal.
There were some «gaps» in the brain circuitry of experimental mice, and the addition of rat neurons was designed to help restore its function. The experiments may help neuroscientists better understand how the brains of different animals develop and how cells of different species integrate.
Such knowledge is not only applicable to rodents; it could help produce «chimeric» pigs with human organs that could be used for transplantation to humans.
FILLING VACANT «NICHES»
The journal Nature also reports on a series of experiments by another scientific team: molecular biologists from the University of Texas Southwestern Medical Center in Dallas. They decided to check how the «mix» of rat and mouse neural cells will behave at very early stages of organism development.
To start, the experts engineered genes in a group of mice in such a way as to destroy some of the neurons of the animals’ olfactory system. This disrupted the circuits linking olfactory neurons in the nose to higher regions of the brain. As a result, the mice were unable to use their sense of smell to find food, which the researchers hid in different places in their cells.
The scientists then took rat stem cells and placed them in blastocysts — mouse embryos at an early stage of development. When they developed into full-grown adults, it turned out that the planted cells filled the gaps in the brain circuits — the mice were perfectly oriented by smell and easily found hidden food.
Now a group of scientists are working on the development of more effective and targeted methods of such hybridization. The researchers believe that the rat cells are able to embed in the vacated «niches» of the organism of another species, not only in the places of olfactory chains of the mouse. They can settle in different parts of the bodies of a wide variety of animals.
IT’S NOT THAT SIMPLE
Biologists have already developed a more aggressive strategy for introducing rat cells into the mouse brain. To do this, they used C-CRISPR technology, a genetic editing tool that cuts genes in several places to ensure their complete inactivation.
The researchers completely destroyed a group of genes in mouse blastocysts that control the development of the forebrain, a significant region that plays an important role in coordinating the animal’s behavior.
Without the forebrain, the blastocysts did not have time to develop into adult mice and died almost immediately after birth. But when the scientists introduced rat stem cells into this «niche» of the blastocyst, the forebrain was fairly quickly regenerated from this foreign material.
The mice did not die, and when they grew up, they were quite healthy. Observation of their behavior showed that it was impossible to find any differences between the «chimeras» and normal mice. Colleagues of Texan scientists from Stanford University in California reached the same conclusion.
In their laboratory, they once tried to make mice «smarter» by planting rats’ brain cells in their bodies. However, the mice did not «get smarter» or «dumber» from this. They showed the usual behavior. Perhaps the differences can be detected statistically, but for this, we will have to test the behavior of a large number of hybrid animals.
ON THE WAY TO «HUMAN-MOUSE»
The scientists say they had long-standing concerns about the development of chimeras. First of all, there is the possibility of transplanting animal tissues or organs, such as pigs, into humans. In addition to ethical considerations, there has been speculation that the human body would reject a transplanted chimeric organ. The latest research is designed to dispel some of the doubts, although not all of them.
The fact is that scientists injected rat cells at a very early stage of development of mice — long before the embryos have formed an immune system. That is when the bodies of animals have not learned to recognize cells as foreign and, therefore, do not attack them. Another problem is a mismatch in developmental rates, with different species having different rates.
Scientists have found that rat cells follow the «clock» of mouse development. The brains of mice develop at the same rate as normal, rather than the slower pace typical of rats. Interestingly, a few years ago, physiologists at the University of Buffalo in New York also conducted similar experiments. But only with human material.
They designed a mouse embryo, which was supposed to contain up to 4% of human cells. As a result, the embryo began developing human red blood cells on day 17 of gestation — much earlier than these cells develop in human embryos. This suggests that human cells also follow the molecular instructions of their host.
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In any case, the technology will continue to improve. Scientists plan to create chimeras by transplanting cells from wild rodent species into laboratory mice. Wild animals, in general, are difficult to study because they are hard to keep and breed in captivity. The new hybrids will help researchers study how the brains of not only rodents but other animals develop and function.
Original research: Rat neurons repair mouse brains — and restore sense of smell
