Zebrafish Amyotrophic Lateral Sclerosis Models

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive loss of motor neurons in the brain and spinal cord, leading to paralysis and death. To better understand ALS, animal models are essential. About 10% of ALS cases are caused by mutations in specific genes, while the remaining 90% of ALS cases are sporadic for unknown reasons. To understand how mutations in SOD1 lead to ALS, mouse models have been generated and have been widely used to study the onset, progression, and treatment of ALS. These animals exhibited hindlimb tremors, progressive weakness, dyskinesia, paralysis, and premature death. While these are useful, mouse models do have some drawbacks, such as mice are highly inbred, which may affect disease progression and phenotype; some strains express very high levels of mutant proteins, which may not accurately reflect human situation; and drug screening in mice is expensive.

The zebrafish is an excellent organism for modeling neurological diseases because of its conserved but simplified vertebrate nervous system, the ability to make transgenes and targeted knockout animals. Furthermore, for the study of motor neuron disease, zebrafish provide accessible motor neurons that can be manipulated in vivo, making them highly relevant for conducting cell-autonomous studies, electrophysiology, and imaging.

Fig.1 Pathological changes in spinal cord and muscle of transgenic sod1 zebrafish.

Our Zebrafish Amyotrophic Lateral Sclerosis Models

Creative Biogene chose to use zebrafish genomic regions containing the endogenous sod1 promoter and sod1 gene to generate zebrafish expressing transgenic mutant Sod1. These fish can recapitulate the major phenotypes of ALS, including neuromuscular junction defects, decreased endurance, motor neuron loss, and muscle pathology. Furthermore, the onset and progression of the disease phenotype in these zebrafish models is variable, reflecting as closely as possible the natural state of the disease, as seen in humans. Our zebrafish models will facilitate further studies of early changes in neuromuscular system and motor neuron physiology during disease progression. If you would like to learn more about the zebrafish ALS models, please feel free to contact us.

Advantages

• Real-time neuroimaging in zebrafish
• Gene functional analysis at specific time points
• Simple and efficient manipulation of multiple genes at a physiologically relevant level
• Suitable for cell manipulation and drug or genetic screening

References

1. Ramesh T, et al. A genetic model of amyotrophic lateral sclerosis in zebrafish displays phenotypic hallmarks of motoneuron disease. Dis Model Mech. 2010, 3(9-10):652-662.
2. Morrice JR, Gregory-Evans CY, Shaw CA. Modeling Environmentally-Induced Motor Neuron Degeneration in Zebrafish. Sci Rep. 2018, 8(1):4890.
3. Asakawa K, Handa H, Kawakami K. Illuminating ALS Motor Neurons With Optogenetics in Zebrafish. Front Cell Dev Biol. 2021, 9:640414.

For research use only. Not intended for any clinical use.