Mucopolysaccharidosis Animal Model Service
Protheragen provides comprehensive, highly customized animal model services for mucopolysaccharidosis, a group of lysosomal storage diseases. We support the pharmaceutical and biotechnology industries by delivering reliable, well-characterized in vivo models that faithfully recapitulate human mucopolysaccharidosis pathology, accelerating your drug discovery and preclinical development programs from target validation through to pharmacodynamic studies.
Overview of Mucopolysaccharidosis Animal Models
Mucopolysaccharidoses represent a group of rare, genetically inherited metabolic disorders originating from the deficiency of particular lysosomal enzymes crucial for the glycosaminoglycans (GAGs) stepwise degradation. The consequences of GAGs accumulation are progressive cellular dysfunction and a plethora of multi-system (organ) pathologies. In order to formulate novel therapeutics, encompassing enzyme replacement therapy (ERT), gene therapy, and small molecules, the research community needs reliable and predictive animal models. These models are critical in understanding the disease mechanisms, assessing the biodistribution, evaluating the efficacy, and establishing the long-term safety.
Fig.1 A characteristic phenotype of the Naglu KO model is hepatomegaly. (Petrova, R., et al., 2023)Our Services
Leveraging our deep expertise in rare disease biology and advanced genetic engineering capabilities, we offer an integrated preclinical service platform. Our strength lies in our ability to provide not just animal models, but a complete suite of services built around validated models, including comprehensive phenotypic characterization, molecular and biochemical analysis, histopathological assessment, and drug testing. This end-to-end approach ensures that you receive high-quality data to de-risk your drug development pipeline and make informed decisions.
Animal Models of Mucopolysaccharidosis
Protheragen offers a portfolio of well-established animal models that accurately model the various mucopolysaccharidosis subtypes. Our models are primarily generated via targeted genetic engineering to disrupt specific genes, mirroring the human genetic defects.
Optional models:
- Idua knockout model
- Ids knockout model
- Sgsh knockout model
- Naglu knockout model
- Galns knockout model
- Others
Mouse Model for Mucopolysaccharidosis Research
| Model Name | Modeling Method | Sales Status | Detailed Description |
|---|---|---|---|
| Arsb-KO Mouse Model | Knockout | Embryo Cryopreservation | Exon 2 of the Arsb gene is deleted for the generation of Arsb knockout mice. |
| Atg7-Flox Mouse Model | Conditional knockout | Sperm Cryopreservation | These mice harbor loxP sites that flank exon 5-6 of the Atg7 gene. |
| Atp7b-Flox Mouse Model | Conditional knockout | Sperm Cryopreservation | These mice have loxP sites flanking exon 2 of the Atp7b gene. |
| Atp7b-H1071Q Mouse Model | Point Mutation | Sperm Cryopreservation | These mice possess an H1071Q mutation in the Atp7b gene. |
| Galns-KO Mouse Model | Knockout | Sperm Cryopreservation | Galns knockout mice are generated by deleting exons 2-4 of the Galns gene. |
| Gns-KO Mouse Model | Knockout | Embryo Cryopreservation | Gns knockout mice are generated through the deletion of exons 3-7 in the Gns gene. |
| Gusb-Flox Mouse Model | Conditional knockout | Repository Live | These strains feature loxP sites flanking exon 2-8 of the Gusb gene. |
| Gusb-KO Mouse Model | Knockout | Repository Live | Gusb knockout mice are created by deleting exons 2-8 of the Gusb gene. |
| Hyal1-KO Mouse Model | Knockout | Embryo Cryopreservation | Hyal1 knockout mice are generated by deleting exon 2 of the Hyal1 gene. |
| Ids-KO Mouse Model | Knockout | Sperm Cryopreservation | Ids knockout mice are generated by deleting exons 3-4 of the Ids gene. |
| Idua-Flox Mouse Model | Conditional knockout | Sperm Cryopreservation | These mice contain loxP sites that flank exon 4-13 of the Idua gene. |
| Idua-KO Mouse Model | Knockout | Sperm Cryopreservation | Idua knockout mice are generated by deleting exons 4-13 of the Idua gene. |
| Naglu-KO Mouse Model | Knockout | Sperm Cryopreservation | Naglu knockout mice are produced by deleting exon 3 of the Naglu gene. |
| NCG-Idua-W392X Mouse Model | Knock-in | Repository Live | A point mutation introduced in exon 10 causes a W392X mutation in the Idua protein. |
| Sgsh-Flox Mouse Model | Conditional knockout | Sperm Cryopreservation | These mice have loxP sites flanking exons 3-6 of the Sgsh gene. |
| Sgsh-KO Mouse Model | Knockout | Sperm Cryopreservation | Sgsh knockout mice are produced by deleting exons 3-6 of the Sgsh gene. |
Case Study-Ids-KO Mouse Model Development
Model Introduction
The Ids-knockout (Ids-KO) mouse model, established on a C57BL/6 background, represents a robust and well-validated preclinical model for mucopolysaccharidosis type II. This model completely lacks iduronate 2-sulfatase (IDS) protein expression, leading to the manifestations of hallmark mucopolysaccharidosis type II pathologies, including systemic GAG accumulation and multi-organ dysfunction. As such, it provides a critical in vivo platform for rigorous evaluation of novel therapeutic candidates.
Methodology
- Animal Model: An Ids-KO mouse model was generated on a C57BL/6 background via gene editing technology to disrupt the Ids gene. Wild-type (WT) mice were maintained as controls. All animals were housed under specific pathogen-free conditions with a standard diet.
- Phenotypic Analysis Methods: A comprehensive phenotypic characterization was conducted. Tissue weights (liver, spleen) were measured and normalized to body weight. GAG levels were quantified in urine samples and in tissue homogenates (heart, liver, spleen, lung, kidney, brain). Histopathological analysis was performed on liver tissues fixed in formalin, embedded in paraffin, sectioned, and stained with Hematoxylin and Eosin (H&E) for microscopic evaluation.
Phenotypic Analysis & Results
Comprehensive phenotypic analysis confirmed the model's relevance; Ids-KO mice exhibited significant phenotypic abnormalities consistent with human mucopolysaccharidosis type II pathology. A significant increase in the liver-to-body weight (LW/BW) and spleen-to-body weight (SW/BW) ratios was detected in 16-week-old Ids-KO mice, indicating pronounced hepatosplenomegaly. Biochemical analysis confirmed systemic GAG storage, with a significant increase in total GAG content in the urine of Ids-KO mice at 16 weeks of age. Furthermore, tissue-specific GAG concentrations were markedly elevated in all examined organs, including the liver, heart, spleen, lung, kidney, and brain of Ids-KO mice. H&E staining of liver tissue from Ids-KO mice revealed prominent cytoplasmic vacuolization, a classic histopathological sign of lysosomal storage.
Fig. 2 Phenotypic characterization of the Ids-KO mouse model. (A-B) Significant increase in the LW/BW and SW/BW ratios in Ids-KO mice, indicating hepatosplenomegaly. (C) Markedly elevated urinary GAG content in 16-week-old Ids-KO mice. (D) Significant accumulation of GAGs in all major tissues examined. Data are presented as mean ± SEM (n=5; ***p < 0.001, *p < 0.05).Conclusion
The collective data from the Ids-KO model firmly establish its high relevance and validity for mucopolysaccharidosis type II research. This model successfully recapitulates key disease hallmarks, including systemic GAG accumulation, hepatosplenomegaly, and characteristic cellular pathology. These findings robustly validate the Ids-KO mouse as a reliable and predictive tool for preclinical drug development. We utilize this well-characterized model within our integrated research platform to research drug efficacy and safety, thereby de-risking and accelerating the translation of promising therapeutics from bench to bedside.
Contact Us
Protheragen's end-to-end service is designed to be your strategic partner in mucopolysaccharidosis research. Our capabilities include detailed pharmacokinetics studies to understand your therapeutic's absorption, distribution, metabolism, and excretion, as well as rigorous drug safety and toxicology evaluations to identify potential adverse effects. We are committed to providing the reliable, high-quality services you need to advance your promising mucopolysaccharidosis therapy. Contact us to discuss your specific project requirements and how we can collaborate to accelerate your research timeline.
Reference
- Petrova, Ralitsa et al. "Disease pathology signatures in a mouse model of Mucopolysaccharidosis type IIIB." Scientific reports 13.1 (2023): 16699.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.