动物造模,神经变性病动物模型 zi-bio 2024-02-28 628

　　Animal models are very valuable in helping us understand the pathogenesis of neurodegenerative diseases and find treatment methods. Compared to rodents, large animals are closer to humans and provide a good model for identifying important pathological events observed in humans; Large animals are also crucial for validating effective treatment methods or determining treatment targets. Due to the lack of embryonic stem cell lines from large animals, it is difficult to construct large-scale animal models of neurodegenerative diseases using traditional gene targeting techniques.

　　In recent years, CRISPR/Cas9 has been successfully applied to genetic modification of genomes of different species. Recently, Dr. Li Xiaojiang from the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, published a review article in the international academic journal Molecular Neurogeneration (impact factor 6.563), discussing the use of CRISPR/Cas9 technology to construct large-scale animal models that can more realistically simulate human degenerative diseases.

　　In the first half of 2015, researcher Li Xiaojiang's research group published multiple academic papers in international authoritative journals such as Human Molecular Genetics, Neuron, PLOS Genetics, and Journal of Neuroscience, using animals such as mice and macaques as models to analyze the molecular mechanisms of age-related neurodegenerative diseases. One of the studies, published in Human Molecular Genetics in April, utilized the CRISPR/Cas9 system to functionally disrupt the muscular dystrophy protein genes in macaques, highlighting the possibility of using CRISPR/Cas9 to effectively prepare large animal models of human diseases.

　　Neurodegenerative diseases - Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and frontotemporal dementia (FTD) - all exhibit age dependent and selective neurodegenerative changes. With the extension of human lifespan, these neurodegenerative diseases have a higher incidence rate; However, the pathogenesis of most of these neurodegenerative diseases is still unclear, and we still lack effective treatment methods for these important brain diseases.

　　In this review, the author points out that transgenic methods and CRISPR/Cas9 can be used to prepare large-scale animal models of diseases, such as non-human primate models of neurodegenerative diseases. CRISPR/Cas9 is a novel genome modification tool that can effectively and easily target any gene in reproductive and somatic cells of different species. Therefore, CRISPR/Cas9 can achieve genome editing of non-human primates and large animals to generate gene mutations and faithfully mimic the pathology of human patients.

　　Due to the ability of CRISPR/Cas9 to disrupt two alleles, this system allows us to use the first construction method