Mouse made from two fathers
Chinese researchers have successfully engineered a mouse with two male parents.
The bi-paternal mouse survived to adulthood, according to a study published in Cell Stem Cell.
It marks a significant advance in reproductive biology and genetic engineering.
Mammalian reproduction typically requires genetic contributions from both a male and a female due to genomic imprinting, a process that regulates gene activity depending on whether a gene is inherited from the mother or father.
This imprinting ensures proper embryonic development, and its disruption has long been a barrier to unisexual reproduction.
Led by Wei Li of the Chinese Academy of Sciences, the research team used embryonic stem cell engineering to modify 20 imprinting genes, employing techniques such as frameshift mutations and gene deletions.
These changes not only enabled some bi-paternal embryos to develop to adulthood but also resulted in more stable pluripotent stem cells, which are crucial for cloning and regenerative medicine.
“The unique characteristics of imprinting genes have led scientists to believe that they are a fundamental barrier to unisexual reproduction in mammals,” said co-corresponding author Qi Zhou.
Previous attempts to create bi-paternal mice had failed, with embryos halting development due to imprinting-related abnormalities.
The latest study overcame those limitations by correcting imprinting errors at key loci, including the Sfmbt2 gene cluster, which is vital for placenta formation.
Researchers found that deleting specific imprinted regions allowed for functional placental development, a crucial step toward sustaining bi-paternal embryos to term.
Despite these advances, challenges remain.
Only 11.8 per cent of viable embryos reached birth, and most had severe developmental defects. The few that survived to adulthood exhibited altered growth patterns, a reduced lifespan, and sterility.
However, the findings suggest a potential path toward refining imprinting corrections for broader applications in stem cell and cloning research.