26 January 2018

The first "real" primate clones

The first monkeys cloned according to the "Dolly sheep method" were born in China

"The Attic"

The first primates cloned by somatic cell nucleus transfer (SNCT) were born at the Institute of Neurobiology of the Chinese Academy of Sciences in Shanghai.

Crab-eating macaques (Macaca fascicularis) named Zhong Zhong and Hua Hua were born by Caesarean section in December 2017. Now the monkeys are being artificially fed, growing and developing in accordance with age norms.

Zhong Zhong and Hua Hua are not the first clones among primates. The first cloned monkey was the Rhesus Tetra macaque – back in 1992. However, the Tetra was cloned in a simpler way, dividing the embryo in the same way as twins appear in nature. This method can produce no more than four genetically identical descendants.

Now, for the first time, Chinese scientists have managed to apply the somatic cell nucleus transfer method on primates, and at the same time viable offspring were born. 23 species of mammals have already been cloned using this technology, including sheep, cows, pigs, mice, rats, rabbits, cats and dogs. In particular, with his help, the famous Dolly lamb was born. However, it was not possible to clone primates in this way before – the embryo did not take root in the uterus of the surrogate mother.

The technology of cloning by transferring the nucleus of a somatic cell consists in the fact that scientists remove the nucleus from the egg and place the nucleus of a differentiated somatic (non-reproductive) cell in it. Then, as soon as possible, the egg is transplanted to a surrogate mother, and a clone of the cell that was the donor of the nucleus develops from the egg.

According to scientists, all earlier attempts to use this technique for cloning monkeys were unsuccessful due to incorrect reprogramming of the somatic cell nucleus, and it is necessary for the further development of the transplanted embryo. Chinese scientists optimized the transplant protocol, in particular, used the nuclei of fetal fibroblasts – connective tissue cells obtained from embryos, and used trichostatin A, a substance that has powerful differentiating properties in mammalian cell culture, which significantly increased the chance of embryo development.

Thus, during the transplantation of fetal fibroblast nuclei, six embryos from 21 monkeys took root, and it was from these embryos that Zhong Zhong and Hua Hua developed. When scientists used the nucleus of the egg-bearing mound cells (the epithelial cells of the follicle surrounding the eggs) for transplantation, 22 embryos out of 42 took root, but only two monkeys were born, who died 3 and 30 hours after birth from respiratory failure.

Genetic analysis confirmed that the nuclear DNA and mitochondrial RNA of Zhong Zhong and Hua Hua originated from the nucleus of the donor cell and the egg of the surrogate mother, respectively. Scientists plan to further optimize the technique of core transplantation using fetal fibroblasts and, of course, observe how Zhong Zhong and Hua Hua grow and develop.

Cloned monkeys are an ideal model for studying processes peculiar only to primates (including humans) that occur with brain disorders, metabolic and immunological disorders, and oncological diseases.

Such cloning will help to create whole populations of genetically identical monkeys on which it will be possible to conduct a wide range of biomedical research, including testing new drugs. The results of the study are published in the journal Cell (Liu et al., Cloning of Macaque Monkeys by Somatic Cell Nuclear Transfer).

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