In a First, Mouse Pups with Two Dads Live to Adulthood

Amazing stuff! 😊

"... Now, after spending almost six years improving their method, the same research team, led by developmental biologist Wei Li at the Chinese Academy of Sciences (CAS), has successfully generated mouse pups from two male parents, with some surviving into adulthood. The results, published in Cell Stem Cell, uncover mechanisms that can advance the generation of genetically modified animal models and improve understanding of some congenital diseases. ...

In the present study, the researchers took a closer look at the nonviable pups to determine what was going wrong. They observed physical abnormalities such as excessive weight, open tongue, umbilical hernias, and genetic abnormalities like overexpression of paternally expressed imprinted genes. Researchers have previously hypothesized that paternal genes promote growth, while maternal genes restrict it. Consistent with this, Li and his team observed that excessive organ growth in bi-paternal pups compressed their chest cavity, resulting in death. ..."

"... Earlier attempts to make a bi-paternal mouse used ovarian organoids to derive oocytes from male pluripotent stem cells; those ooctyes were then fertilized with sperm from another male. However, when the homologous chromosomes—the chromosomes that divide during meiosis to create oocytes and sperm—originated from the same sex, imprinting abnormalities arose, leading to severe developmental defects.  ..."

From the highlights and abstract:

"Highlights

• Bi-paternal mice reaching adulthood generated via targeted imprinting modifications

• ESCs with imprinting modifications showed twice the developmental ability of control

• Functional bi-paternal placenta created by modifying the Sfmbt2 microRNA cluster

• Mice with 20 loci modifications exhibited higher cloning efficiency

Summary

Imprinting abnormalities pose a significant challenge in applications involving embryonic stem cells, induced pluripotent stem cells, and animal cloning, with no universal correction method owing to their complexity and stochastic nature.

In this study, we targeted these defects at their source—embryos from same-sex parents—aiming to establish a stable, maintainable imprinting pattern de novo in mammalian cells. Using bi-paternal mouse embryos, which exhibit severe imprinting defects and are typically non-viable, we introduced frameshift mutations, gene deletions, and regulatory edits at 20 key imprinted loci, ultimately achieving the development of fully adult animals, albeit with a relatively low survival rate.

The findings provide strong evidence that imprinting abnormalities are a primary barrier to unisexual reproduction in mammals. Moreover, this approach can significantly improve developmental outcomes for embryonic stem cells and cloned animals, opening promising avenues for advancements in regenerative medicine."

In a First, Mouse Pups with Two Dads Live to Adulthood | The Scientist "By using genetic material from two male mice, researchers successfully created pups that survived to adulthood, offering insights into unisexual reproduction in mammals."

First mouse with two male parents to reach adulthood

Adult bi-paternal offspring generated through direct modification of imprinted genes in mammals (open access)

Graphical abstract