The adult male mice that have fathers and went to their own descendants
Yanchang Wei
For the first time, the mice with two parents continued to obtain their own offspring – which represents a big step towards enabling two men to have children with genetically associated with them. However, there is still a long way to cut it before it can be tried in people.
Yanchang Wei At the University of Shanghai Jiao Tong, China has achieved this feat by placing both sperm cells in an egg whose nucleus was removed. Then the team used a method called Epigenome to re -program seven sites in the DNA sperm, which was necessary to allow the fetus to develop.
Of the 259 of these embryos that were transferred to female mice, only two of the offspring – both of them are male – and grew to adulthood, making the success rate very low. Both of them at that time – which seemed natural in terms of size, weight and appearance – after mating with females.
The creation of mice with two parents has proven much more difficult than creating mice with two nations. The birth of the first fertile mouse with two nationsKaguya, was reported in 2004.
Kaguya should have been genetically modified, but in 2022, Wei and his colleagues managed to Create only a similar father with an Epigenome editing onlyWhich does not change the DNA sequence. This same method was used to make mice without a mother.
The reason is that it is important to create mammals with two parents or mothers A phenomenon called fingerprintAnd, which is associated with the fact that most animals have two groups of chromosomes, one inherited from the mother and one of the father.
During the formation of eggs and sperm, chemical stickers are added to these chromosomes that conclude some genes to be active and others to be inactive. These “Lagine” changes are called because they do not change the basic DNA sequence, but it is still possible to pass stickers when the cells are divided, which means that their effects can last for life.
Decally, the Lagine programming in mothers is different from those in parents, with some genes that have been classified as “operation” in sperm that are classified as “outside” in eggs, and vice versa.
This means that if the egg has two groups of mother chromosomes, or two groups of parental, it cannot develop naturally. The gene that should be active in one chromosome may be turned off in both, or both copies of the gene may be active when it is only one, which leads to an “overdose” of this gene.
In the Kaguya case, the researchers toured this by deleting part of the gene to make genetics in general more natural. But creating mice with two parents requires many changes.
Earlier this year, a separate team in China I got a few mice with two parents to grow to adulthood After making 20 genetic amendments to normalizing genetic activity, but these mice were not completely healthy or fertile.
Although correcting genetic activity through genetic modification is useful for studying the fingerprint in laboratory animals, it will be unacceptable in people, not the least that the effects of genetic changes are not fully understood.
For their Lagini approach, Wi and his team used modified forms of Crisper Proteins that are usually used to release genes. Just like standard CRISPR proteins, they can be manufactured to search for specific locations on genomics. But when these sequences are found, modified proteins add or remove lagin stickers instead of changing the DNA.
The study says a big step forward Helen O’Neel At the University of London. “It confirms that the genetic fingerprint is the main obstacle to monochromatic reproduction in mammals and shows that it can be overcome.”
Since it does not involve a genetic amendment, it can be used in principle to allow couples of the same sex to have genetic children. However, the success rate should be much higher before the technique is considered for use in people. “While this research is about generating offspring of parents of the same sex, it cannot be perceived to translate it into humans because of the large number of eggs required, the large number of women are the necessary alternatives and the low success rate,” he says. Christophe Gallichett At the Sainsbury Wellcome Center in the United Kingdom.
There are several reasons that make the success rate very low. For beginners, the combination of sperm cells means that a quarter of the fetuses had a chromosomes and will not develop far away. Also, Epigenome editing only in all seven sites made a small percentage of fetuses, and may have traces outside the target in some cases.
Success rate and health Animals are likely to be improved by changing more than seven sites, but perhaps this will not be translated into people because sites that need a change are likely to be different from those in mice.
If human children who have parents have ever created in this way, they will do technically To be a three -year -old children Because mitochondria in its cells, which contains a small amount of DNA, will come from the donor with eggs.
In 2023, a team announced in Japan The birth of mouse puppies with two parents using a third technique The conversion of the mouse stem cells includes eggs. However, it is not clear whether any result has survived from adulthood, and yet no one has been able to convert human stem cells into eggs.
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