Genetically engineered pig models of neurological diseases

Abstract

Genetically modified animal models are commonly used for in vivo studies of human diseases. Mice are the most common animal models used in biomedical research, which have provided important insights into disease pathogenesis and are widely used to find treatments for diseases. However, due to the differences in the anatomical structure and physiological function between human and mouse brains, most genetically modified mouse models cannot fully recapitulate the overt and selective neuronal loss seen in age-dependent neurodegeneration diseases. While non-human primates (NHP) are closer to humans and have been used to model human disease, these models are difficult to be utilized at a large scale due to various limitations including their high costs, prolonged breeding time, community concerns for use of NHP, and high ethical standards. As an important animal resource in agriculture, pigs are also used as animal models in biomedical research. The central nervous system of pigs is highly similar to that of humans, making pig models suitable for investigating neurological diseases. The relatively short breeding period, large litter size, and established somatic cell transfer technology are advantages over NHP for using pigs to model human diseases. The recent development of gene editing tools allows one to more efficiently generate pig models that can precisely mimic genetic mutations in neurological diseases. In this review, we summarize recent advances in the use of pigs for modeling human neurological diseases, including new approaches for generating genetically modified pig models.