Fig.1 In vivo and in vitro models for Niemann-Pick disease type C1 research. (Zhang, C., et al., 2024)Leveraging advanced technologies, we offer a comprehensive suite of genetically engineered animal models for Niemann-Pick disease. Our fully customized solutions generate precise models with knockout, knock-in, and conditional knockout for the SMPD1, NPC1, and NPC2 genes, designed to meet your specific research objectives.
Optional models:
- Npc1-/- mouse model
- Npc2-/- mouse model
- Smpd1 knockout model
- Others
Mouse Model for Niemann-Pick Disease Research
| Model Name | Modeling Method | Sales Status | Detailed Description |
|---|---|---|---|
| Npc1-Flox Mouse Model | Conditional Knockout | Repository Live | These mice carry loxP sites flanking exon 9 of the Npc1 gene. When crossed with a Cre recombinase-expressing strain, this model enables tissue-specific knockout of the Npc1 gene. |
| Npc1-KO Mouse Model | Knockout | Sperm Cryopreservation | Deletion of exon 9 in the Npc1 gene produces a constitutive knockout mouse model. |
| Npc2-Flox Mouse Model | Conditional Knockout | Sperm Cryopreservation | Exon 3 of the Npc2 gene is the targeted region for generating a conditional knockout model. |
| Smpd1-Flox Mouse Model | Conditional Knockout | Sperm Cryopreservation | These strains carry loxP sites flanking exons 1-2 of the Smpd1 gene, enabling tissue-specific gene inactivation upon Cre crossbreeding. |
| Smpd1-KO Mouse Model | Knockout | Sperm Cryopreservation | Deletion of exons 1-2 in the Smpd1 gene generates a Smpd1 constitutive knockout mouse. |
Case Study-Npc1-/- Mouse Model Development
Model Introduction
The Npc1-/- mouse model is a genetically engineered model widely recognized as a well-established and highly relevant preclinical tool. It accurately recapitulates the progressive hepatic dysfunction and neurological decline characteristic of Niemann-Pick disease type C, thereby providing a critical platform for evaluating the efficacy of novel therapeutic interventions.
Methodology
- Animal Model: Starting at postnatal day 7, one group of Npc1-/- mice received weekly intraperitoneal injections of a therapeutic agent, while sham-treated Npc1-/- control groups were administered equal volumes of vehicle solution at corresponding time points.
- Phenotypic Analysis Methods: All mice were deeply anesthetized and subjected to exsanguination via inferior vena cava puncture for immediate plasma separation. The liver was then harvested, weighed, and processed for further analysis. Plasma activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), key biomarkers of hepatocellular injury, were quantified spectrophotometrically. Concurrently, liver tissue samples were fixed in formalin, embedded in paraffin, sectioned, and stained with Hematoxylin and Eosin (H&E) following standard protocols for comprehensive morphological evaluation.
Phenotypic Analysis & Results
Body and liver weight measurements revealed a significant 1.3-fold increase in the liver-to-body weight ratio (LW/BW) in Npc1-/- mice compared to wild-type (WT) controls. Drug therapy markedly reduced this ratio, restoring it to levels comparable to those in WT mice. Histological analysis of liver tissue from Npc1-/- mice showed evident necrosis and significant lipid accumulation in hepatocytes. In contrast, livers from drug-treated Npc1-/- mice exhibited clear pathological improvement, characterized by markedly reduced necrosis and lipid deposition. Consistent with histological observations, the significantly elevated plasma AST and ALT levels in Npc1-/- mice were substantially lowered by drug therapy, returning to values within the WT control range.
Fig. 2 Drug therapy ameliorates hepatic pathology in Npc1-/- mice. Therapy with the therapeutic agent normalized liver weight, as indicated by the liver-to-body weight ratio (A), and significantly reduced plasma levels of hepatocellular damage markers AST (B) and ALT (C). Data are presented as mean ± SEM (n=5; *p < 0.05).Conclusion
These data demonstrate that the Npc1-/- mouse model exhibits a robust and quantifiable hepatic phenotype that effectively mirrors key aspects of human Niemann-Pick disease type C liver disease. The significant therapeutic response to drug therapy, evidenced by normalized serum biomarkers and improved histopathology, validates the utility of this model for rigorous preclinical efficacy testing. Our integrated service platform offers this well-validated model, combined with detailed phenotypic and molecular analyses, to reliably support drug discovery and development efforts targeting Niemann-Pick disease type C.
Contact Us
Protheragen's service encompasses the entire preclinical workflow, from initial model development to conducting sophisticated therapeutic efficacy studies. We are equipped to perform detailed pharmacokinetics and pharmacodynamics analyses to understand your drug candidate's behavior in the diseased model, and we conduct comprehensive drug safety and toxicology evaluations. Partner with us to enhance the quality and impact of your Niemann-Pick disease research efforts. Contact us today to discuss your project requirements.
Reference
- Zhang, Caifeng et al. "Advances in research on potential therapeutic approaches for Niemann-Pick C1 disease." Frontiers in pharmacology 15 (2024): 1465872.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.