The technical milestone, presented on January 25 in the journal Cell, makes it a realistic possibility for labs to conduct research with customizable populations of genetically uniform monkeys. The academy in a news statement on its website said. “There are a lot of questions about primate biology that can be studied by having this additional model,” says senior author Qiang Sun, Director of the Nonhuman Primate Research Facility at the Chinese Academy of Sciences Institute of Neuroscience. “You can produce cloned monkeys with the same genetic background except the gene you manipulated. This will generate real models not just for genetically based brain diseases, but also cancer, immune or metabolic disorders, and allow us to test the efficacy of the drugs for these conditions before clinical use.”

Zhong Zhong and Hua Hua are not the first primate clones—the title goes to Tetra, a rhesus monkey made in 1999 by a simpler method called embryo splitting (Science, v. 287, no. 5451, pp. 317-319). This approach is how twins are made, but can only generate up to 4 offspring at a time. Zhong Zhong and Hua Hua are the product of somatic cell nuclear transfer (SCNT), the technique used to create Dolly the sheep over 20 years ago, in which researchers remove the nucleus from an egg cell and replace it with another nucleus from differentiated body cells. This reconstructed egg then develops into a clone of whatever donated the replacement nucleus.

Differentiated monkey cell nuclei, compared to other mammals such as mice or dogs, have proven resistant to SCNT. Sun and his colleagues overcame this challenge primarily by introducing epigenetic modulators after the nuclear transfer that switch on or off the genes that are inhibiting the embryo development.

The researchers found their success rate increased by transferring nuclei taken from fetal differentiated cells, such as fibroblasts, a cell type in the connective tissue. Zhong Zhong and Hua Hua are clones of the same macaque fetal fibroblasts. Cells from adult donor cells were also used, but those babies only lived for a few hours after birth.

“We tried several different methods but only one worked,” says Sun. “There was much failure before we found a way to successfully clone a monkey.”

The researchers plan to continue improving the technique, which will also benefit from future work in other labs, and monitoring Zhong Zhong and Hua Hua for their physical and intellectual development. The babies are currently bottle fed and are growing normally compared to monkeys their age. The group is also expecting more macaque clones to be born over the coming months.

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Though the CHGA promoter haplotypeis present in other ethnic populations, it occurs more frequently in population of South Asian ancestry. “It is a protein of neuroendocrine origin and is secreted along with hormones like catecholamines. Earlier studies had suggest edits role in regulation of cardiovascular and metabolic diseases but there was no data aboutit in South Asian population,” said Lakshmi Subramanian, first author of this paper.

“Westudied genomic DNA of Indians and discovered a specific set of changes in the CHGA genesequence called Haplotype2 which contributed to increased CHGA gene expression, and ultimately increased CHGA protein levels in plasma. When the clinical parameters of those in the study were compared, Haplotype2 carriers displayed higher levels of metabolic and cardiovascular traits like plasma glucose, blood pressure and body mass index,” explained Dr. Nitish R. Mahapatra, Professor at IIT Madras.

However, he said, these results need further validation in animal models as well as large scale studies in individuals with metabolic syndrome. “We hope these findings would help unravel biological pathways and mechanisms underlying these complex diseases and would help in the development of therapeutic as well as preventive strategies,” said Dr. Mahapatra.

“Basic research in cardiovascular biology is in a very nascent stage in India with only a handful of researchers working in this field. This new study significantly contributes towards understanding molecular basis of cardiovascular and metabolic diseases. This is a fast emerging area with tremendous therapeutic and diagnostic potential,” commented Dr Shyamal K. Goswami, a professor at School of Life Science, JNU, who is not connected with the study.

The study was led by Dr. Mahapatra in a collaborative effort with Dr. Ajit S. Mullasari at Madras Medical Mission, Chennaiand Dr. Madhu Khullar at PGIMER, Chandigarh.

(Article shared from India Science Wire)

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