A study describing programmed chromosome ligation in mice that resulted in the creation of new and sustainable karyotypes in the lab is published in Science this week, demonstrating the feasibility of chromosome-level engineering in mammals. While chromosome engineering has been successfully performed in yeast, it remains a challenge in higher eukaryotes. In earlier work, a team led by researchers from the Chinese Academy of Sciences found that the deletion of three imprinted chromosomal regions allowed for the establishment of a stable sperm-like imprinting pattern in haploid embryonic stem cells. In the new study, the scientists used these cells and gene editing to fuse the two largest mouse chromosomes — chromosomes 1 and 2 — and two medium-size chromosomes — chromosomes 4 and 5 — resulting in karyotypes with three different arrangements. "Chromatin conformation and stem cell differentiation were minimally affected," the authors write. "However, karyotypes carrying fused chromosomes 1 and 2 resulted in arrested mitosis, polyploidization, and embryonic lethality, whereas a smaller fused chromosome composed of chromosomes 4 and 5 was able to be passed on to homozygous offspring." The results, they write, points to a potential route for large-scale engineering of endogenous or exotic DNA in mammals.
Sustainable Chromosome-Level Engineering in Mice
Aug 26, 2022