24 January 2019

Clones with a disturbed circadian rhythm

Chinese scientists have cloned a CRISPR monkey for the first time

Olga Dobrovidova, N+1

Chinese scientists edited the genome of a crab-eating macaque using the CRISPR/Cas9 method, and then cloned it, obtaining five more monkeys.

In addition to demonstrating the technology of cloning CRISPR animals, they are planned to be used for research of diseases associated with circadian rhythm disorders, the report says. Science China Press. The story is also told by the Chinese state agency Xinhua.

The new clones were obtained at the Institute of Neuroscience of the Chinese Academy of Sciences in Shanghai by the same method as the cubs of Zhong Zhong and Hua Hua, only instead of fibroblasts of the aborted embryo, scientists managed to use fibroblasts of a young monkey. The donor of the nuclei was a macaque with a knockout BMAL1 gene, "disabled" using the CRISPR/Cas9 genome editing method at the embryo stage. The results of genome editing and cloning of monkeys are described in two articles in the journal National Science Review.

First, Chinese specialists edited the genome of 88 embryos, which were planted in 31 females — 10 of them became pregnant, and as a result eight animals were born (two pregnancies ended in miscarriages). Of the eight animals, five had mutations in the gene needed by scientists, two of them had mosaicism (the mutation was not present in all cells of the body). As a result, Chinese researchers chose macaque A6 as a donor. Then 65 females were planted with 325 embryos with transplanted nuclei, 16 of them successfully became pregnant, and as a result, scientists received only five clones with mutations in BMAL1 in both alleles and without mosaicism.

monkeys.png
Five resulting Macaque A6 clones
(from an article in National Science Review)

As noted in the reports, the donor and cloned monkeys demonstrate behavior characteristic of circadian rhythm disorders: they sleep less, are more active and mobile at night, their daily cycles of hormone concentration in the blood are disrupted, anxiety is increased, depressive states and "behavior similar to schizophrenia" occur.

The lead author of one of the articles, Qiang Sun from the Institute of Neuroscience, notes that in this way scientists will be able to create model organisms for studying a variety of genetically determined diseases, from brain diseases to metabolic diseases, the immune system and cancer. The idea of the experimenters is that by developing "designer" monkeys with the necessary mutations and cloning them, it will be possible, among other things, to significantly reduce the number of laboratory animals needed for experiments. The authors of the articles emphasize that the work was carried out in strict accordance with the ethical standards adopted at the Institute.

Earlier, scientists from the Scottish Roslin Institute, where they created the first cloned mammal, Dolly the sheep, said that they plan to use the CRISPR genetic editing method to edit the chicken genome so that the bird is invulnerable to influenza. The researchers hope to get the first chicken in 2019.

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