Advances in Mouse Models of Amyotrophic Lateral Sclerosis
10.12300/j.issn.1674-5817.2024.161
- VernacularTitle:肌萎缩侧索硬化症小鼠模型研究进展
- Author:
Lianlian LUO
1
;
Yanchun YUAN
2
;
Junling WANG
2
;
Guangsen SHI
1
Author Information
1. Zunyi Medical University, Zhuhai 519000, China
2. Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China
- Publication Type:Journal Article
- Keywords:
Amyotrophic lateral sclerosis;
Neurodegenerative diseases;
Genetic factors;
Genetic mutations;
Mouse models
- From:
Laboratory Animal and Comparative Medicine
2025;45(3):290-299
- CountryChina
- Language:Chinese
-
Abstract:
Amyotrophic lateral sclerosis (ALS) is an irreversible, fatal neurodegenerative disorder whose incidence is positively correlated with the aging population. ALS is characterized by the progressive loss of motor neurons, leading to muscle weakness, atrophy, and ultimately respiratory failure. The pathogenesis of ALS involves multiple factors, including genetic and environmental influences, with genetic factors playing a particularly significant role. To date, several causative genes have been identified in ALS, such as the Cu/Zn superoxide dismutase 1 (Cu/Zn SOD1, also known as SOD1) gene, transactive response DNA-binding protein 43 (TDP-43) gene, fused in sarcoma (FUS) gene, and chromosome open reading frame 72 (C9orf72). Mutations in these genes have been found not only in familial ALS but also in sporadic ALS. Based on the identified ALS risk genes, various ALS animal models have been established through multiple approaches, including transgenic models, gene knockout/knock-in models, and adeno-associated virus-mediated overexpression models. These models simulate some typical pathological features of human ALS, such as motor neuron loss, ubiquitinated inclusions, and neuromuscular junction degeneration. However, these models still have limitations: (1) single-gene mutation models are insufficient to fully replicate the complex multi-factorial pathogenesis of sporadic ALS; (2) significant differences in microenvironmental regulation mechanisms and the rate of neurodegeneration between model organisms and humans may affect the accurate reproduction of disease phenotypes and the reliable evaluation of drug efficacy. To better understand the pathogenesis of ALS and promote the development of effective therapies, constructing and optimizing ALS animal models is crucial. This review aims to summarize commonly used ALS gene mutation mouse models, analyze their phenotypes and pathological characteristics, including transgenic mouse models, gene knockout/knock-in mouse models, and adeno-associated virus-mediated overexpression mouse models, and further discuss their specific applications in ALS pathogenesis research and drug development by comparing the advantages and limitations of each model.
