Huntington's disease is an autosomal dominant inherited neurodegenerative disorder affecting the basal ganglia and cerebral cortex. It is a rare and fatal progressive neurodegenerative disease, with most patients exhibiting a progressive course of the disease due to dysfunction of the brain's neural functions.

Mice have been widely used to study the mechanism of Huntington's disease and search for clinical treatments, but many therapeutic drugs that are effective in mouse models are not clinically effective in patients.

HD is caused by a single gene mutation that results in an expansion of CAG repeats on exon 1 of the HTT gene, a protein with multiple roles that is uniquely and highly expressed in the nervous system, and is characterized by a preferential loss of midspine neurons in the striatum. This is an ideal disease model, which is the basis for the study of polygenic mutations. Using CRISPR/Cas9 and somatic cell nuclear transfer technology, the HD gene knock-in pig model was constructed.

1. 1.The knock-in (KI) porcine model of Huntington's disease more realistically reproduces the neurodegeneration seen in HD patients.

2. 2.We demonstrate for the first time that the pronounced and selective neurodegeneration observed in HD patients can be recapitulated by endogenously expressing a mutant protein in a large mammal.

3. 3.Rodent models provide valuable tools for studying the pathogenesis of neurodegenerative diseases, while porcine models are important tools for validating basic discoveries and therapeutic targets.

4. 4.The HDKI porcine model shows obvious neurodegeneration and can serve as an ideal model for treatment trials of stem cell therapy to replace degenerated neurons in neurodegenerative diseases.

5. 5.Evidence of lesions in the HD KI porcine model provides a basis for establishing animal models to mimic selective neurodegeneration in other key neurodegenerative diseases such as AD and PD and effective therapeutic strategies.