A sustainable mouse karyotype created by programmed chromosome fusion

Chromosome engineering has been attempted successfully in yeast but remains challenging in higher eukaryotes, including mammals. Here, we report programmed chromosome ligation in mice that resulted in the creation of new karyotypes in the lab. Using haploid embryonic stem cells and gene editing, we fused the two largest mouse chromosomes, chromosomes 1 and 2, and two medium-size chromosomes, chromosomes 4 and 5. Chromatin conformation and stem cell differentiation were minimally affected. 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. Our results suggest the feasibility of chromosome-level engineering in mammals.

Automated summary

This study reports successful programmed chromosome ligation in mice, leading to the creation of new karyotypes. By fusing chromosomes 1 and 2, as well as chromosomes 4 and 5, using haploid embryonic stem cells and gene editing, the researchers were able to generate new chromosome combinations. The fused chromosome pairs had minimal impact on chromatin conformation and stem cell differentiation. However, the fused chromosomes 1 and 2 resulted in mitotic arrest, polyploidization, and embryonic lethality, while the smaller fused chromosome composed of chromosomes 4 and 5 could be passed on to homozygous offspring.