New pathogenic insights from large animal models of neurodegenerative diseases.
10.1007/s13238-022-00912-8
- Author:
Peng YIN
1
;
Shihua LI
1
;
Xiao-Jiang LI
1
;
Weili YANG
2
Author Information
1. Guangdong Key Laboratory of Non-human Primate Research, Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, 510632, China.
2. Guangdong Key Laboratory of Non-human Primate Research, Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, 510632, China. weiliyang12@jnu.edu.cn.
- Publication Type:Research Support, Non-U.S. Gov't
- Keywords:
CRISPR/Cas9;
large animal models;
neurodegenerative diseases
- MeSH:
Amyotrophic Lateral Sclerosis/genetics*;
Animals;
Brain/pathology*;
Disease Models, Animal;
Gene Editing;
Neurodegenerative Diseases/pathology*;
Swine
- From:
Protein & Cell
2022;13(10):707-720
- CountryChina
- Language:English
-
Abstract:
Animal models are essential for investigating the pathogenesis and developing the treatment of human diseases. Identification of genetic mutations responsible for neurodegenerative diseases has enabled the creation of a large number of small animal models that mimic genetic defects found in the affected individuals. Of the current animal models, rodents with genetic modifications are the most commonly used animal models and provided important insights into pathogenesis. However, most of genetically modified rodent models lack overt neurodegeneration, imposing challenges and obstacles in utilizing them to rigorously test the therapeutic effects on neurodegeneration. Recent studies that used CRISPR/Cas9-targeted large animal (pigs and monkeys) have uncovered important pathological events that resemble neurodegeneration in the patient's brain but could not be produced in small animal models. Here we highlight the unique nature of large animals to model neurodegenerative diseases as well as the limitations and challenges in establishing large animal models of neurodegenerative diseases, with focus on Huntington disease, Amyotrophic lateral sclerosis, and Parkinson diseases. We also discuss how to use the important pathogenic insights from large animal models to make rodent models more capable of recapitulating important pathological features of neurodegenerative diseases.
