Amyotrophic Lateral Sclerosis (ALS) Animal Model Service
Animal models of amyotrophic lateral sclerosis (ALS) recapitulate key disease features such as motor neuron degeneration and progressive paralysis, enabling mechanistic studies and therapeutic screening of this devastating disease. Protheragen leverages deep expertise in ALS animal model development to deliver tailored solutions and accelerate preclinical ALS therapeutic discovery.
Overview of Amyotrophic Lateral Sclerosis (ALS) Animal Models
Animal models are indispensable for advancing our understanding of amyotrophic lateral sclerosis (ALS) and developing effective therapies. These models, primarily developed in rodents such as mice and rats, aim to recapitulate the genetic mutations (e.g., in SOD1, C9orf72, TARDBP) and pathological hallmarks of human ALS, including motor neuron degeneration, neuroinflammation, and protein aggregation. Through rigorous phenotypic characterization, these models provide a critical platform for investigating disease mechanisms, validating therapeutic targets, and conducting preclinical efficacy and safety testing of potential treatments.
Fig.1 Animal models of amyotrophic lateral sclerosis (ALS). (Zhou L, et al., 2024)
Types of Amyotrophic Lateral Sclerosis (ALS) Animal Models
Animal models are crucial for amyotrophic lateral sclerosis (ALS) research, and they can be broadly classified into three main types based on their design and induction methods: transgenic models, knock-in models, and chemically-induced models. Each type offers unique advantages for studying specific aspects of ALS pathology and therapeutic development.
Transgenic Models
Transgenic models are created by introducing a foreign gene, often a mutant human ALS-associated gene (e.g., SOD1, TARDBP), into the animal's genome. These models, such as the widely used SOD1-G93A mouse, exhibit rapid and robust motor neuron degeneration, glial activation, and progressive paralysis.
Knock-in Models
Knock-in models involve replacing the animal's native gene with a human ALS-causing mutation (e.g., C9orf72 repeat expansion) using precise gene editing techniques. These models maintain endogenous gene regulation, resulting in more physiologically relevant and gradual disease progression.
Chemically-Induced Models
Chemically-induced models utilize neurotoxins, such as β-methylamino-L-alanine (L-BMAA), to trigger ALS-like symptoms, including motor neuron loss and oxidative stress. These models are primarily used to simulate sporadic ALS (sALS) and study environmental contributions to the disease.
Our Services
At Protheragen, we provide comprehensive and sophisticated animal model development services for amyotrophic lateral sclerosis (ALS) research, empowering scientists worldwide to accelerate the discovery of novel therapeutic interventions. Our team delivers highly validated, pathologically accurate ALS models using advanced technologies and deep expertise, providing a robust foundation for disease mechanism studies, biomarker identification, and drug efficacy testing.
Animal Models of Amyotrophic Lateral Sclerosis (ALS)
Genetically Engineered Models
Utilizing advanced technologies such as gene editing and transgenesis, our scientists are dedicated to developing precise genetically engineered models to replicate the genetic basis of amyotrophic lateral sclerosis (ALS).
- FVB-C9orf72 BAC Mouse Model
- C9orf72 Knockdown Zebrafish Model
- SOD1-G93A Mouse Model
- G93R-mSOD1 Zebrafish Model
- TDP43-Q331K Mouse Model
- TDP43-A315T Zebrafish Model
Induced Models
Induced models focus on mimicking aspects of sporadic amyotrophic lateral sclerosis (sALS) and exploring environmental factors contributing to the disease. We utilize neurotoxins such as bisphenol A (BPA) to induce ALS-like pathology in wild-type animals, including motor neuron stress, glial activation, and oxidative damage.
- Bisphenol A (BPA)-induced Zebrafish Model
- β-Sitosterol-β-d-glucoside (BSSG)-induced Mouse Model
Featured Animal Models
| Model Name | Modeling Method | Sales Status | Detailed Description |
| R26-CAG-LSL-hSOD1*G94A-IRES-EGFP Mice | Transgenic | Sperm Cryopreservation | A CAG-FRT-LSL- SOD1 (G94A)-IRES-EGFP-WPRE-pA expression cassette was knocked into the Rosa26 locus. |
| R26-SA-Loxp-PGK-Neo-Loxp-Pik3ca-H1047R Mice | Transgenic | Sperm Cryopreservation | SA-Loxp-PGK-Neo-pA-Loxp-Pik3ca-H1047R-pA expression cassette was knocked into the Rosa26 locus. |
| Raf1-D486N Mice | Knock-in | Embryo Cryopreservation | These mice carry a p.D486N mutation of Raf1 gene. |
| Rag1-KO (Rag1-EGFP) Mice | Knockout | Repository Live | A Rag1 knockout model was constructed by knocking a loxP-EGFP-PolyA-loxP-Neo-loxP expression cassette into the start codon of the Rag1 gene. These mice exhibit severe immunodeficiency, with a severely reduced number of peripheral blood T and B lymphocytes, reaching levels comparable to or lower than those of nude mice. They are highly sensitive to subcutaneous tumor implantation and growth, potentially replacing nude mice and NOD-SCID mice as tumor-bearing mouse models. |
Case Study-TDP43ΔNLS Mouse Model
- Species: Mice were produced by crossing a tetO-hTDP-43-ΔNLS line 4 with a NEFH-tTA line 8.
- Modeling Method: This cross breeding created a mouse model with tetracycline-repressible TDP-43 which lacks the nuclear localization signal. When the tetracycline analogue, Doxycycline, is removed from the diet of bigenic animals, toxic mislocalisation of TDP-43 into the cytoplasm of neurons is induced. Mice were genotyped using a standard PCR assay. Mice expressing only the tTA gene were designated as control animals, whilst mice expressing both the NEFH-tTA and TetO promoter (bigenic) were designated as TDP43ΔNLS animals exhibiting symptoms of sALS.
- Experimental Method: We confirmed the ALS-like phenotype using simple behavioral tests. In the two-minute tail suspension test, mice are gently suspended by their tails for up to two minutes, and their hind limb extension is observed. In the grip strength endurance test, mice are placed on a metal grid which is gently shaken to encourage them to grip on. They are then placed upside down on a soft surface, and the endurance time that the mouse can hold on for is recorded (up to two minutes).
Fig.2 (A) Image of a control mouse, showing a healthy splayed limb phenotype. (B) Image of a TDP43ΔNLS mouse model, showing a severe clasping phenotype affecting all 4 limbs. (C) Two-tailed T-test bar graph representation of grip strength endurance test showed a significant decrease in mean cage lid holding time in the TDP43ΔNLS mouse model compared to non-transgenic controls (t(10)=71.499, p<0.001).
To advance the treatment of rare motor neuron diseases, Protheragen provides comprehensive animal model development services to facilitate preclinical drug research, including pharmacodynamics (PD), pharmacokinetics (PK), and toxicology studies. If you are interested in our animal model development services, please do not hesitate to contact us for more details and quotation information.
Reference
- Zhou L, Xie M, Wang X, et al. The usage and advantages of several common amyotrophic lateral sclerosis animal models[J]. Frontiers in Neuroscience, 2024, 18: 1341109.