At first glance, seven creations around their cages look like other mice. But they have an unusual lineage. They were born as DNA of two dads. The mouse joined the animals of the elite group born by the same -sex parents and opened a way for testing in large animals such as monkeys.
The results led by Wei Li and Qi Zhou, the veteran reproductive researcher of the Chinese Academy of Sciences, wrote the Lluís Montoliu in Madrid’s National Biotechnology Center, who did not participate in the study.
The mice with two dads were previously born, but scientists used a completely different strategy in this study, which provided insight into reproductive mysteries. In the process of “imprint”, some genes of the embryo are turned on or off, depending on whether they are biologically mother or dad. Injacker problems often stop growth by damaging embryos.
In a new study, the team hunted the genes imprinted in the embryos made from same -sex parents and painted the complex “fingerprint” of the pattern. Then we zeroed 20 genes and used them to tinker with them using CRISPR. After hundreds of experiments, the edited embryo comes from two male donors, from the birth of seven young cubs grown as an adult.
Imprinting does not affect reproduction only. The hiccups of this process can also damage biotechnology that depends on embryonic stem cells, animal cloning or induced multifunctional stem cells (IPSC). The team wrote that the change of imprints is complicated and difficult to predict because of the “universal modification method”.
LI said in a press release: “This work will help to solve the limitations of stem cells and regenerative medicine.
Genetic Civil War
Cardinal rules of reproduction in mammals still meet sperm. But now, beyond the design of nature, there are more options for the source of these germ cells. Thanks to the IPSC technology that turns skin cells in the same state as stem cells, laboratory-anesthesia eggs and sperm cells are now possible.
Scientists manipulated functional eggs and ovarians and created mouse puppies born from same -sex parents. LI’s team created the first mice born from two mothers in 2018. Compared to my colleagues, the mouse was small, but I could live longer and be a mother.
The height was to unlock the snippet of the engraved code.
Eggs and sperm each have half of our DNA. But when two sources of DNA meet, you can match your head. For example, a similar part of the mother’s gene code can encode a small baby for easier births, while Dad’s people can encode a larger and stronger offspring for better survival. In other words, it is important to maintain both balance.
Montoliu wrote that embryos made in same -sex games are “not surviving naturally.”
Evolution has a solution. By blocking some DNA, the descendants only have a genetic activity from the mother or dad. This trade off can interfere with the DNA “Civil War” of the initial embryos and grow. LI’s team hunted three essential DNA areas related to imprint and deleted the letters with a mother’s DNA using CrisPR. The editing was wiped out of the mark and essentially transformed the cells into a phase-spur, which led to a healthy baby mouse when injecting eggs.
But this process was not effective for both dads. Here, the goal was to erase the marks imprinted in male donor cells and turn them into similar eggs. Despite editing up to seven genes that control the imprint, only about 2 %of the efforts led to the date of birth. None of the puppies survived until they became adults.
Double Dad
It is notorious to make offspring from two men, so it fails much faster than the embryos with two mothers’ DNA.
Scientists used skin cell -derived IPSC to create cells from male donors. However, when the previous study was modified as a donor sperm, the laboratory egg led to an initial embryo with serious imprinting problems. After being delivered to the surrogate mother, we developed a defect that would eventually end. The result suggests that the normal imprint of the balance of the genetic expression of mom and dad is important for the embryos to prosper.
There are currently about 200 stamped genes related to embryonic development. Here the team aimed at 20 to edit genes.
In a complex series of experiments, they first created “half -cell cells.” These cells include only half of male donors. Using CRISPR, the team has modified each engraving site individually to terminate the activity of the relevant genes. Some editing completely deleted the genes. Others added mutations to suppress the function. More genetic editing for “regulatory” DNA weakened their activities.
The result was Frankenstein cells similar to Gamete, but carried half of the genome and disappeared. Next, scientists injected the cells edited with normal sperm (“parent donor”) with eggs that removed nuclear and DNA. The resulting eggs now have a full DNA set, each of which comes from male parents.
The approach worked until time. When I was transplanted as a surrogate mother, part of the initial embryo grew up as a mouse puppy. Seven people eventually reached adults. Genetic adjustment also improved the placenta health, the previous obstacle of mouse research with same -sex parents.
Guan-Zheng Luo, a research author of Sun Yat-Sen University, said, “This discovery provides strong evidence that abnormal mammal fasting reproduction.
This work is added to previous studies that made puppies from both dads. The scientist team led by Katsuhiko Hayashi of Osaka University, the scientist team, used the curiosity of IPSC deformation at the chromosome level. This is a completely different way from what we pursue in the current study. The mouse grew up as an adult and ate his dog.
Montoliu said at the meeting, when he first shared these results, he said, “It was left and left without breath.”
The mouse of the new research has suffered a hard time. They have a larger frame, the nose squeaky and wider hair. Often signatures related to the imprint of parents. They also had less anxiety when roaming open fields, larger and larger than expected. The hippocampus of each mouse, a brain area related to learning, memory and emotions, was smaller than usual. And they had a much shorter life.
Given this problem, this method is rarely suitable for clinical application. Manipulating genes in human reproductive cells is now forbidden in many countries.
In other words, Martin Leeb of Max Perutz Labs Vienna said, “This task is impressive in technical complexity. Chemistry and Engineering NewsPeople who are not involved in research. “I personally thought that more genetic engineering was needed to be born.”
The team explores other genetic adjustments to further improve the process and learn more about imprints. On the other hand, they plan to expand the method to monkeys, and his reproduction is much more similar to us.
