Hereditary Spastic Paraplegia (HSP) Animal Model Service
Hereditary spastic paraplegia (HSP) animal models are genetically engineered organisms that recapitulate key pathological features of human HSP, such as corticospinal tract degeneration and progressive motor deficits. At Protheragen, we specialize in developing highly accurate HSP animal models to accelerate preclinical research for potential therapeutics. Our expertise ensures that your studies are supported by the most reliable models, streamlining your drug development journey.
Introduction to Hereditary Spastic Paraplegia (HSP) Animal Models
Animal models are indispensable tools for deciphering the complex pathophysiology of hereditary spastic paraplegia (HSP) and advancing therapeutic strategies. By replicating causative mutations in genes such as SPAST, ATL1, and REEP1 in organisms like mice and rats, these models recapitulate the hallmark progressive degeneration of the corticospinal tract axons, leading to spastic paraparesis. They provide a controllable in vivo system to study disease mechanisms and serve as a key platform for rigorous preclinical testing of potential drugs and genetic interventions.
Fig.1 Phenotypic characterization of Cyp2u1-/- mice. (Parodi L, Pujol C., 2022)
Challenges in Hereditary Spastic Paraplegia (HSP) Animal Model Development
The development of biologically relevant animal models for hereditary spastic paraplegia (HSP) is fraught with significant challenges that stem from the disease's inherent genetic complexity and unique pathophysiology. Successfully replicating the human condition in a model organism requires overcoming hurdles related to genetics, phenotypic manifestation, and translational relevance.
- Genetic Diversity: With over 80 known causative genes, developing models requires creating custom, mutation-specific designs for each target, which is resource-intensive.
- Slow Disease Progression: Reproducing the human condition's gradual "dying-back" axonopathy in short-lived rodents is difficult, often resulting in delayed, subtle, or absent phenotypes.
- Phenotyping Complexity: Detecting spasticity and axonopathy requires sophisticated, costly techniques like automated gait analysis and electrophysiology, as overt symptoms are often lacking.
- Translation Gaps: Fundamental biological differences between rodents and humans can limit the predictive value of models for therapeutic outcomes in clinical trials.
- Variable Presentation: Mirroring the human traits of incomplete penetrance and varying symptom severity in genetically uniform animal strains is a significant hurdle.
Our Services
To overcome the significant challenges in hereditary spastic paraplegia (HSP) animal model development, Protheragen provides a comprehensive, end-to-end solution designed for precision, reliability, and translational relevance. We leverage our deep expertise in neurogenetics and advanced gene editing to deliver fully validated models that accurately recapitulate the human disease, enabling you to bypass technical bottlenecks and accelerate your therapeutic discovery pipeline.
Animal Models of Hereditary Spastic Paraplegia (HSP)
- Reep1 Knockout Mouse Model
- Spastin (SPASTC448Y) Transgenic Mouse Model
- SPG11 Knockout Mouse Model
- ZFYVE26 Knockout Mouse Model
- Cyp2u1-/- Mouse Model
- More
Plp1-Flox Mice for Hereditary Spastic Paraplegia (HSP) Research
| Model Name | Plp1-Flox Mice |
| Model Type | Genetically Engineered Mouse Model (GEMM) |
| Modeling Method | Conditional Knockout |
| Targeted Disease | Hereditary Spastic Paraplegia Type 2 (SPG2) |
| Sales Status | Embryo Cryopreservation |
| Detailed Description | These mice carry loxP sites flanking Exon 3 of Plp1 gene. When crossed with a Cre recombinase-expressing strain, this strain is useful in eliminating tissue-specific conditional expression of Plp1 gene. |
| Applications & Therapeutic Areas | The study of glial cell differentiation and the susceptibility pathway of sudden infant death syndrome (SIDS). |
Case Study-Spg11 Knockout (Spg11−/−) Mouse Model
- Species: C57BL/6J Mouse
- Modeling Method: The Spg11−/− mouse model was established using targeted gene knockout technology, in which key exons of the Spg11 gene were deleted to generate a loss-of-function allele. This model recapitulates the key features of spastic paraplegia type 11 (SPG11).
Fig.2 In open field (OF) analysis, male Spg11−/− mice walked longer distances (A) and showed a higher movement duration (B) at 6 and 18 months of age compared with wild-type (WT) mice, indicating hyperactive-like behavior.
Specializing in comprehensive preclinical assessment, Protheragen develops precise and reliable animal models for pharmacodynamics (PD), pharmacokinetic (PK), and toxicology studies to accelerate the therapeutic development for hereditary spastic paraplegia (HSP). If you are interested in our animal model development services, please do not hesitate to contact us for more details and quotation information.
Reference
- Parodi L, Pujol C. Hereditary spastic paraplegia type 56: what a mouse can tell-a narrative review[J]. Journal of Bio-X Research, 2022, 5(02): 55-63.