Scientists have used the gene-editing tool, CRISPR/Cas9 gene editing to create a pig model of Huntington’s disease (HD), which is to be used for drug testing. 

We know that 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. 

Despite genetically modified mice having been used in the past to model neurodegenerative diseases, they lack the typical neurodegeneration or overt neuronal loss seen in human brains. Therefore, animal models that can provide a far more accurate reflection of the progression of neurodegenerative diseases, are in demand. 

A team of scientists led by Professor Li Xiao-Jiang at Emory University School of Medicine, U.S., in collaboration with researchers from Jinan University and the Chinese Academy of Sciences in Guangzhou, took this on board. As a result, they used genetic engineering to establish a pig model of HD. The results of this study have been published in the journal Cell

The researchers used the CRISPR/Cas9 gene editing technique to introduce a segment of a human gene encoding mHTT into pig fibroblast cells. Somatic cell nuclear transfer was also performed to generate pig embryos carrying the specific genetic alteration. 

The team noticed that the genetically altered pigs displayed symptoms of neurodegeneration, including some movement problems. They also exhibited respiratory difficulties, which resemble those experienced by humans with HD. These particular symptoms cannot be observed in mouse models of HD, suggesting that the pig model more accurately mirrors human HD. In addition, the pigs also experienced 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 Professor 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’ translate well in humans.”

The researchers also reported, that when 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. In comparison with non-human primate models, the pigs do also offer advantages of faster breeding and larger litter sizes, the researchers added.