This is a group of mice of “two fathers” that were successfully raised to adulthood in an experiment. (Image credit: Zhi-kun Li et al.)
Researchers in China have developed a new way to breed twin mice that allows the offspring to survive to adulthood.
This isn’t the first time scientists have crossed mice with two fathers; a Japanese research team did it in 2023 using a different method. In the new study, published Tuesday (January 28) in the journal Cell Stem Cell, the scientists not only crossed mice with two fathers that survived to adulthood, but they did it in a way that could shed new light on the complex set of genes whose activity changes depending on which parent they’re inherited from. Problems with these genes, known as “imprinted genes,” can cause a variety of disorders in humans, including Angelman syndrome.
“I’m excited about this work — I think it’s an important step,” said Keith Latham, a professor of animal science and obstetrics, gynecology, and reproductive biology at Michigan State University who was not involved in the study. “It’s another significant step forward in understanding the biology of imprinting,” he told Live Science.
Altering “imprinted” genes
In a 2023 study, Japanese scientists collected skin cells from adult male mice and converted them into stem cells that could be used to create eggs. Using an ingenious technique, the team ensured that each of these eggs had two X chromosomes — the pairs of sex chromosomes typically found in females. The team then fertilized these resulting eggs with sperm from male mice, ultimately creating a small number of offspring whose genes came exclusively from male mice.
A new study conducted in China took a different approach to achieve a similar result.
The researchers began by extracting DNA from an immature egg, or oocyte, taken from a female mouse. They then injected the egg with sperm to produce unique stem cells that are found only in embryos. These embryonic stem cells, along with sperm from a male mouse, then implanted into a second egg. This eventually resulted in a fertilized egg that could develop into a baby mouse with DNA from both fathers.
As a key step, the scientists made 20 genetic changes to the stem cells’ DNA. These changes alter the activity of imprinted genes, which have a unique feature: offspring inherit two copies — one from their mother and one from their father — but only need one copy to function. So in each cell, one copy of each imprinted gene is turned off, while the other copy remains active.
This process is called “genomic imprinting,” and when it goes wrong, imprinting disorders occur, leading to problems with growth and development. If you try to create embryos with DNA from two fathers, you get a lot of these imprinting problems because too many of the paternal genes remain active and there are no maternal genes to compensate.
“Our method directly targets imprinted genes that have long been thought to play a central role in bipaternal reproductive barriers,” which makes it difficult for two male parents to create offspring, study co-author Zhi-kun Li, an associate professor at the Chinese Academy of Sciences in Beijing, told Live Science in an email.
In a previous study, Li and his team tweaked just seven imprinting points, or “loci,” in the genome and created mouse fetuses that survived pregnancy, but the mice died after birth, Li noted. The mice had abnormalities such as umbilical hernias, protruding tongues, and enlarged internal organs.
Systematically, researchers identified the genetic causes of each of these problems and introduced more and more genetic
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