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Chinese scientists create pig model of Huntington's disease

Source: Xinhua| 2018-03-30 02:10:20|Editor: Zhou Xin
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CHINA-SCIENCE-HUNTINGTON'S DISEASE-PIG MODEL (CN)

In this photo handed out by the Chinese Academy of Sciences, members of a research team on the world's first pig model for Huntington's disease pose for a group photo at Jinan University in Guangzhou, south China's Guangdong Province, March 28, 2018. A Chinese team of scientists has established a pig model of Huntington's disease (HD), an inherited neurodegenerative disease, using genetic engineering technology. In a study published in "Cell" on Thursday, researchers anticipated that the pigs could be a practical way to test treatments for HD, which is caused by a gene encoding a toxic protein that causes brain cells to die. (Xinhua)

WASHINGTON, March 29 (Xinhua) -- A Chinese team of scientists has established a pig model of Huntington's disease (HD), an inherited neurodegenerative disease, using genetic engineering technology.

In a study published in Cell on Thursday, researchers anticipated that the pigs could be a practical way to test treatments for HD, which is caused by a gene encoding a toxic protein that causes brain cells to die.

Although genetically modified mice have been used widely to model neurodegenerative diseases, they lack the typical neurodegeneration or overt neuronal loss seen in human brains, according to corresponding author Li Xiaojiang, professor of human genetics in Jinan University and who runs a lab at Emory University School of Medicine.

The pig HD model is an example that suggests large animal models could better model other neurodegenerative diseases, such as Alzheimer's and Parkinson's.

A HD pig could be an opportunity to test if the CRISPR-Cas9 gene editing technique can work in larger animals before clinical applications in humans.

Li said, in comparison with mice, treatments for affected nervous system tissues could be better tested in pigs, because their size is closer to that of humans. The pig model of HD also more closely matches the symptoms of the human disease.

Compared with non-human primate models, the pigs offer advantages of faster breeding and larger litter sizes, the researchers said.

Li collaborated with his colleagues at Jinan University and Chinese Academy of Sciences in Guangzhou. The pigs are now housed in Guangzhou.

"In pigs, the pattern of neurodegeneration is almost the same as in humans, and there have been several treatments tested in mouse models that didn't translate to human," said a co-senior author Li Shihua, professor of human genetics at Emory University School of Medicine.

Symptoms displayed by the genetically altered pigs include movement problems. They show respiratory difficulties, which resemble those experienced by humans with HD and are not seen in mouse models of HD.

In addition, the pigs show degeneration of the striatum, the region of the brain most affected by HD in humans, more than other regions of the brain.

Huntington's disease is caused by a gene encoding a toxic protein (mutant huntingtin or mHTT), and mHTT contains abnormally long repeats of a single amino acid, glutamine. Symptoms commonly appear in mid-life and include uncontrolled movements, mood swings and cognitive decline.

Researchers used the CRISPR/Cas9 gene editing technique to introduce a segment of a human gene causing Huntington's, with a very long glutamine repeat region, into pig fibroblast cells.

Then somatic cell nuclear transfer generated pig embryos carrying this genetic alteration. The alteration is referred to a "knock in" because the changed gene is in its natural context.

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