Stem Cells and Gene Editing Create Mice From Two Mothers
Researchers at the Chinese Academy of Sciences have used two female mice to create offspring which subsequently went on to have healthy children of their own. While similar offspring were produced from two male mice, they did not survive for longer than a few days. The work, published in Cell Stem Cell journal, suggests barriers to creating offspring from two parents of the same sex could be overcome with stem cells and targeted gene editing.
When creating the mice with two mothers, the researchers used haploid embryonic stem cells (ESCs), containing half the normal number of chromosomes and DNA from only one parent. The young mice were made by deleting three imprinting regions of the genome from haploid ESCs containing a female parent’s DNA, and injecting them into eggs from another female mouse. In total, 29 live mice were produced from 210 embryos.
Using haploid ESCs means that even before the imprinting regions are removed, the imprinting programming in the cells which causes maternal- or paternal-specific genes to be expressed is reduced. According to co-senior author Baoyang Hu: “We found in this study that haploid ESCs were more similar to primordial germ cells, the precursors of eggs and sperm. The genomic imprinting that’s found in gametes was ‘erased’.”
Twelve living mice were also created from two fathers, using a more complicated procedure. Haploid ESCs containing only a male parent’s DNA were changed to delete seven key imprinted regions. The ESCs were then injected, along with sperm from another mouse, into an egg cell without a nucleus. These embryos were transplanted to surrogate mothers, who carried them. These mice, however, only lived for one or two days, though the researchers expressed a desire to improves the process to ensure bipaternal mice live on to adulthood.
The researchers said challenges remained before they could use the technique in other mammals, such as identifying problematic imprinted genes unique to each species, and concerns for the offspring which die or suffer severe abnormalities.