AsianScientist (Apr. 6, 2018) – Scientists have used CRISPR/Cas9 gene editing to create a pig model of Huntington’s disease (HD) which could be used for drug testing. They published their findings in Cell.
HD is caused by a gene encoding a toxic protein known as mutant huntingtin, or mHTT. mHTT contains abnormally long repeats of a single amino acid, glutamine. The symptoms of HD commonly appear in mid-life and include uncontrolled movements, mood swings and cognitive decline.
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. Hence, animal models that more accurately reflect the progression of neurodegenerative diseases in humans are required.
In the present study, a team of scientists led by Professor Li Xiao-Jiang at Emory University School of Medicine, US, in collaboration with researchers from Jinan University and the Chinese Academy of Sciences in Guangzhou, used genetic engineering to establish a pig model of HD.
The researchers used the CRISPR/Cas9 gene editing technique to introduce a segment of a human gene encoding mHTT into pig fibroblast cells. Subsequently, somatic cell nuclear transfer was performed to generate pig embryos carrying this genetic alteration.
The genetically altered pigs displayed symptoms of neurodegeneration, including movement problems. They also exhibited respiratory difficulties, which resemble those experienced by humans with HD. Such symptoms cannot be observed in mouse models of HD, suggesting that the pig model more accurately mirrors human 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.
“We think the pig model will fill an important gap,” said co-senior author Profesor Li Shihua at Emory University School of Medicine. “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 well in humans.”
The researchers also noted that compared to mice, the delivery of treatments to affected nervous system tissues can be better tested in pigs because the size of their brains is closer to that of humans. Moreover, in comparison with non-human primate models, the pigs offer advantages of faster breeding and larger litter sizes, the researchers said.
Source: Chinese Academy of Sciences; Photo: Shutterstock.
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