Chromosome Engineering Now Possible in Mammals

Previous attempts in chromosome engineering were only successful in yeast, but scientists in China were able to produce the first sustainable engineered karyotype on laboratory mice which now carries two chromosomes fused together.

To achieve this, the scientists fused the two largest mouse chromosomes, labeled chromosomes 1 and 2, and two medium-size chromosomes, labeled chromosomes 4 and 5, using haploid embryonic stem cells and gene editing to program the chromosome ligation in mice and create new karyotypes. In the process, the scientists noted the difficulty in deriving stem cells from unfertilized mouse embryos since the cells only contain one set of chromosomes. But through the concept of genomic imprinting, they figured out that by deleting three naturally imprinted regions, a stable, sperm-like imprinting pattern in cells can be established. This allowed them to fuse chromosomes 4 and 5 head to tail with chromosomes 1 and 2 and create karyotypes in three different arrangements without significantly affecting chromatin conformation and sent cell differentiation. Further testing led to karyotypes carrying fused chromosomes 1 and 2, which resulted in arrested mitosis, polyploidization, and embryonic lethality. On the other hand, a smaller fused chromosome composed of chromosomes 4 and 5 was able to be passed on to homozygous offspring.

This feat allowed a better understanding of how misaligned or malformed chromosomes can be corrected through chromosome engineering in mammals. It also demonstrated that the chromosomal rearrangement event is the basis for species evolution and its importance to reproductive isolation. These findings can unlock possibilities for large-scale DNA engineering in mammals.

More details can be found in Science and EurekAlert!