Scientists in China have unveiled a new method to raise baby mice with two male parents, and the resulting babies can survive in adulthood.
This is not the first time that scientists have raised mice with two dads; A research team in Japan did it in 2023using a different approach. In the new study, published Tuesday, January 28 in the journal Strain cellScientists have not only raised mice with two corpses that could live in adulthood, but have made it in a way that could shed new light on a complex sequence of genes whose activity varies depending on the parent which you inherit them. The problems with these genes, called “printing genes”, can cause a Range of disorders in humansincluding Angelman syndrome.
“I admire the work – I think it’s an important approach,” said Keith LathamProfessor of animal sciences and obstetrics, gynecology and reproductive biology at Michigan State University, which was not involved in research. “This is another important step in understanding the biology of the imprint,” he told Live Science.
Refine “printed” genes
In the 2023 study, Japan scientists collected skin cells of adult male mice and have transformed the skin into stem cells that could be used to grow eggs. Using an intelligent technique, the team made sure that each of these egg cells transported two X chromosomes – the appearance of the sexual chromosome generally found in women. The team then fertilized these resulting eggs with sperm of male mouse, finally generating a small number of descendants whose genes came from male mouse.
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The new study, conducted in China, used a different approach to achieving a similar result.
The researchers began by eliminating the DNA from an immature egg, or oocyte, taken from a female mouse. They then introduced sperm into the egg in order to develop unique stem cells seen only in embryos. These embryonic stem cells, as well as the sperm of a male mouse, are then injected into a second egg. This ultimately gives birth to a fertilized egg which can be transformed into a mouse puppy with DNA of two dads.
As a crucial step, scientists have introduced 20 genetic adjustments into the DNA of stem cells. These adjustments modify the activity of the printing genes, which are unique in that offspring inherits two copies – one of their mom and one of their father – but they only need a copy to work. Thus, in each cell, a copy of each printed gene is closed while the second copy remains functional.
This process is known as “Genomic printing“And when it goes badly, emerging printing disorders, causing growth and development problems. The maternal genes are there to compensate.
“Our approach directly targets printed genes, which have long been suspected of playing a central role in two-way reproductive barriers”, complicating the challenge of generating offspring with two male parents, co-directed author of study Zhi-kun liAn associate teacher at the Chinese Academy of Sciences in Beijing, told Live Science in an email.
In a previous study, Li and colleagues changed only seven hot printing pointsor “LOCI” in the genome, and produced mouse fetuses that have succeeded in pregnancy, but these mice died after birth, said Li. The mice had anomalies, like umbilical hernias, protruding languages and Internal organs extended.
Systematically, the researchers have identified the genetic origin of each of these problems and introduces more and more genetic mouse settings. With 18 modifications, mice needed help in early childhood but could reach adulthood. With 19 adjustments, they had placental growth problems during pregnancy but better succeeded after birth. An additional adjustment – by making 20, in total – seemed to solve this placenta problem.
Interestingly, the imprint seems to be a more important problem to overcome with the two -covered offspring than bimaterral offspring, noted the authors in their report. In their previous work, they were able to raise mice with two mothers who survived adulthood with much less genetic adjustments, just like other research groups. In addition, spontaneous parthenogenesis – in which an egg can become fertilized without sperm – sometimes occurs in animals outside the laboratory.
However, “it is somewhat surprising that the manipulation of only 20 printing genes allows a relatively normal development of two -way embryos where there are hundreds of printing in mice,” said Dr Kotaro SasakiAssociate professor at the School of Veterinary Medicine at the University of Pennsylvania and at the Perelman School of Medicine which was not involved in the work.
However, the resulting mice always had deficits, including a shorter lifespan than normal mice, said Sasaki at Live Science in an email. Experiences have shown that mice were also infertile. On the other hand, the handful of mice that were raised in Japan and survived adulthood were fertile.
“Our next steps include the refinement of the gene editing approach to produce healthier bipan animals,” said Li. It is likely that additional printing genes could be changed to help suffocate health problems remaining, he said. The team also wants to try their approach in additional animal species to see how it translates.
In the long term, this research line could help scientists better understand printing disorders, potentially opening the way to treatments that use Gene edition To repair them in humans, Li suggested.
Latham added that, by better understanding the genetic routes involved, scientists could be able to identify the means to counter the disorders with drugs, rather than the edition of genes. He added that there could also be applications for research in agriculture, if she finally helped breeders cultivate desirable features in cattle, for example.
Regarding humans, Latham said we want to better understand the risks and advantages of the approach before trying to use it in people. Sasaki has echoed the feeling, noting that a number of technological obstacles and ethical dilemmas “all hinder the clinical application in humans in the near future”.