Amazing stuff!
"For the first time, researchers have fused two mouse chromosomes together in vitro, resulting in living mice with new karyotypes. ...
Chromosomal fusions are also common in cancer and have been linked to health issues, including infertility, aneuploidy, and childhood diseases. So, researchers have long sought the ability to precisely manipulate chromosomes in model organisms, especially mammalian ones, in the hopes of investigating fusions from both medical and evolutionary perspectives. ...
To fuse chromosomes in mice, the researchers used a technology they first developed in yeast: briefly, they injected modified haploid mouse embryonic stem cells friend (haESCs) with a CRISPR-Cas9 system that targets and eliminates telomeres and centromeres on two specific chromosomes. As a result, the targeted chromosomes zipped themselves together. ..."
Chromosomal fusions are also common in cancer and have been linked to health issues, including infertility, aneuploidy, and childhood diseases. So, researchers have long sought the ability to precisely manipulate chromosomes in model organisms, especially mammalian ones, in the hopes of investigating fusions from both medical and evolutionary perspectives. ...
To fuse chromosomes in mice, the researchers used a technology they first developed in yeast: briefly, they injected modified haploid mouse embryonic stem cells friend (haESCs) with a CRISPR-Cas9 system that targets and eliminates telomeres and centromeres on two specific chromosomes. As a result, the targeted chromosomes zipped themselves together. ..."
"Designer chromosomes
One of the goals in synthetic biology is to generate complex multicellular life with designed DNA sequences. Being able to manipulate DNA at large scales, including at the chromosome level, is an important step toward this goal. So far, chromosome-level genetic engineering has been accomplished only in haploid yeast. By applying gene editing to haploid embryonic stem cells, Wang et al. achieved whole-chromosome ligations in mice, and successfully derived animals with 19 pairs of chromosomes, one pair fewer than is standard in this species."
From the abstract:
"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."
A sustainable mouse karyotype created by programmed chromosome fusion (no public access)
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