Mice with two fathers have been created using genome editing, and have survived into adulthood .
Researchers at the Chinese Academy of Sciences, Beijing, China, created egg-like cells from male embryonic stem cells, which were then fertilised with sperm from another male. The team genetically modified imprinted genes in the embryonic stem cells to overcome developmental defects associated with bi-paternal reproduction. The work, published in Cell Stem Cell, could aid regenerative medicine research and may improve our understanding of congenital imprinting disorders.
'This work will help to address a number of limitations in stem cell and regenerative medicine research,' said co-corresponding author Professor Wei Li from the state key laboratory of stem cell and reproductive biology at the Institute of Zoology Chinese Academy of Sciences, according to phys.org.
During fertilisation, the two sets of chromosomes from the egg and sperm cells combine to form a diploid zygote. It has two copies of every chromosome – one from the sperm cell and one from the egg cell – that align in a certain way to form the genetics of the resulting organism. This is known as genomic imprinting, and allows genes to be expressed or not, depending on whether they are inherited from the mother or the father.
'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 Professor Qi Zhou, also from the state key laboratory of stem cell and reproductive biology. 'Even when constructing bi-maternal or bi-paternal embryos artificially, they fail to develop properly, and they stall at some point during development due to these genes.'
In a complex series of experiments, researchers identified 20 key imprinted genes leading to fatal developmental defects, including some associated with increased growth. Modifying these genes using the CRISPR genome editing approach increased survival, however, only 12 percent of viable embryos developed until birth. Pups that did survive had abnormal growth, shorter lifespans and were infertile.
Previously, healthy adult mice from two male parents have been generated by a different technique using induced pluripotent stem cells (see BioNews 1182). These mice, produced by a team in Japan, grew normally and were fertile. However, the success rate was low with approximately only one percent of embryos surviving until birth.
Expansion of this type of work into humans is a long way off. However, the results of this study show the importance of genetic imprinting throughout development and highlight a potential therapeutic role for imprinting correction.
'Further modifications to the imprinting genes could potentially facilitate the generation of healthy bi-paternal mice capable of producing viable gametes and lead to new therapeutic strategies for imprinting-related diseases,' said lead author Dr Li Zhi-kun also from the state key laboratory of stem cell and reproductive biology.
Sources and References
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Adult bi-paternal offspring generated through direct modification of imprinted genes in mammals
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Mice born with two fathers - but don't expect the same for people
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Mice with two dads have been created using CRISPR
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Mouse created with two fathers and no mother survives to adulthood
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Mouse with two dads created in major biological breakthrough
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'Motherless' mice created from embryos with only male genes
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