Niemann-Pick Disease (NP) Animal Model Service
Animal models are indispensable in drug development, providing critical insights into a candidate's efficacy, safety, and mechanism of action within a complex living system. With our deep expertise in Niemann-Pick (NP) disease research, Protheragen offers customized animal model development services to help you accelerate the commercialization of NP therapies.
Overview of Niemann-Pick Disease (NP) Animal Models
Animal models of Niemann-Pick (NP) disease, predominantly mice with targeted disruptions in the Smpd1 (modeling Type A/B) or Npc1/Npc2 (modeling Type C) genes, recapitulate key disease pathologies such as visceral lipid accumulation and progressive neurodegeneration, serving as indispensable tools for elucidating disease mechanisms and evaluating potential therapeutic interventions like enzyme replacement, substrate reduction, and novel gene therapies.
Fig.1 A brief overview of the mechanisms and models of Niemann-Pick disease type C1 (NP-C1). (Zhang C, et al., 2024)
Application of Niemann-Pick Disease (NP) Animal Models
- Disease Mechanism Research
- Drug Efficacy Testing
- Gene Therapy Development
- Biomarker Discovery
- Preclinical Trial Design
- More
Our Services
Specializing in animal model development for rare neurometabolic diseases, Protheragen creates highly accurate and validated models for complex diseases like Niemann-Pick (NP) disease. We provide researchers with powerful, customizable preclinical research tools that faithfully recapitulate the genetic and phenotypic characteristics of NP, laying a critical foundation for studying disease mechanisms and evaluating novel therapeutic strategies.
Animal Models of Niemann-Pick Disease (NP)
Spontaneous Mutant Models
As a leader in animal model services, Protheragen provides clients with rigorously validated spontaneous mutant models. Our core strength lies in our expert breeding and colony management program, which guarantees the stable propagation of these models with unparalleled genetic integrity and phenotypic consistency.
- BALB/c Npc1<nih> Mouse Model
- Other Models
Genetically Engineered Models
Protheragen offers a comprehensive suite of genetically engineered models for Niemann-Pick disease (NP) research. We specialize in the creation of precise knockout models, leveraging state-of-the-art gene editing and ES cell targeting technologies to ensure precise gene knockout and accurate phenotypic recapitulation.
- Npc1 Knockout Mouse Model
- Npc2 Knockout Mouse Model
- Npc1 Conditional Knockout Mouse Model
- Npc1 Point Mutation Mouse Model
- Smpd1 Knockout Mouse Model
- Smpd1 Point Mutation Mouse Model
Featured Animal Models
| Model Name | Npc1-Flox Mice |
| Model Type | Genetically Engineered Mouse Model (GEMM) |
| Modeling Method | Conditional Knockout |
| Targeted Disease | Niemann-Pick Disease Type C (NPC) |
| Sales Status | Embryo Cryopreservation |
| Detailed Description | These mice carry loxP sites flanking Exon 9 of Npc1 gene. When crossed with a Cre recombinase-expressing strain, this strain is useful in eliminating tissue-specific conditional expression of Npc1 gene. |
| Applications & Therapeutic Areas | Lipoprotein metabolism and metabolism related research. |
Case Study-Npc1imagine/imagine (I/I) Mouse Model
Model Introduction
Niemann-Pick disease type C (NPC) is a lysosomal storage disorder caused by mutations in the NPC1 gene, resulting in the abnormal accumulation of cholesterol and glycosphingolipids. To advance the study of NPC pathophysiology, we generated the Npc1imagine/imagine (I/I) mouse model, which carries a deep intronic mutation (c.1554-1009G>A) homologous to a pathogenic human variant.
Methodology
- Animal Model: Npc1imagine/imagine (I/I) homozygous mice and wild-type (WT) controls on a C57BL/6 background.
- Modeling Method: First, heterozygous founders were generated by replacing the entire murine Npc1 intron 9 with the human homologous intron containing the c.1554-1009G>A (I) mutation; subsequently, intercrossing of these heterozygotes produced the homozygous Npc1imagine/imagine (I/I) mice.
- Phenotypic Analysis: Comprehensive lipid profiling of brain tissue was performed to quantify key sphingolipid species, including ceramide (Cer), sphingomyelin (SM), dihydroceramide (dhCer), dihydrosphingomyelin (dhSM), glucosylceramide (GlcCer), lactosylceramide (LacCer), and gangliosides (GM1, GM2, GM3, GD1).
Phenotypic Analysis & Results
Comprehensive lipid profiling of brain tissue revealed a pronounced sphingolipid storage phenotype in I/I mice, closely mirroring the lipid trafficking defects observed in human NPC patients.
- Generalized Sphingolipid Accumulation: Compared to WT mice, I/I mice exhibited significant increases in multiple sphingolipid species, including ceramide (Cer), sphingomyelin (SM), dihydroceramide (dhCer), dihydrosphingomyelin (dhSM), lactosylceramide (LacCer), and gangliosides (GM1, GM2, GM3, GD1) (Fig.2).
- Selective Reduction in Glucosylceramide: In contrast, glucosylceramide (GlcCer) levels were significantly decreased in I/I mice, highlighting a distinct disruption in glycosphingolipid metabolism (Fig.2).
Fig.2 Brain lipid storage in I/I mice compared to wild-type (WT) mice. Data are presented as mean ± SD (n=5–8). *p < 0.05, **p < 0.01, ***p < 0.001 vs. WT.
Conclusion
This case study validates the Npc1imagine/imagine (I/I) mouse as a highly relevant model for Niemann-Pick disease type C (NPC) research. The overall sphingolipid profile, characterized by widespread accumulation of intermediate and complex sphingolipids alongside reduced GlcCer, confirms the successful recapitulation of NPC-like lipid dysregulation in this model. This genetically precise and phenotypically accurate system provides a robust platform for investigating disease mechanisms and evaluating novel therapeutic interventions.
Contact Us
Leveraging our well-characterized animal models, Protheragen provides comprehensive pharmacodynamics (PD), pharmacokinetics (PK), and toxicology research services to seamlessly advance your therapeutic candidates. If you are interested in our animal model development services, please do not hesitate to contact us for more details and quotation information.
Reference
- Zhang C, Su K, Jiang X, et al. Advances in research on potential therapeutic approaches for Niemann-Pick C1 disease[J]. Frontiers in Pharmacology, 2024, 15: 1465872.