IgA Nephropathy (IgAN) Model
- Background
- Models
- Study Examples
- Features
- FAQ
Creative Bioarray offers validated IgA nephropathy (IgAN) animal models to support preclinical drug discovery and translational research. Our platform includes ready-to-use induced models as well as customized spontaneous and humanized models, enabling flexible study design for efficacy evaluation and mechanistic investigation.
Overview of IgA Nephropathy (IgAN)
IgA nephropathy (IgAN) is the most prevalent form of primary glomerulonephritis globally, and many patients progress to chronic kidney disease. However, current therapies are merely symptomatic and do not prevent disease progression.
The pathogenesis of IgAN involves multiple steps of immune dysregulation. Hyperactive B-cells lead to production of galactose-deficient IgA1 (Gd-IgA1). These altered proteins prompt the production of autoantibodies that form circulating immune complexes. Deposition of these immune complexes in the glomerular mesangium results in inflammation and activation of the complement system. The result is mesangial proliferation, deposition of extracellular matrix, and scarring of the kidney.
Fig. 1. Pathogenesis of IgA nephropathy (Kai K, 2012).
Available therapies (i.e. RAAS inhibitors, steroids) only target symptoms and their long-term effectiveness is limited with many safety concerns. Therefore, validated IgA nephropathy animal models are crucial for speeding up drug discovery.
Our IgA Nephropathy Animal Models – From Standard Models to Custom Development
BSA/LPS/CCl₄-Induced IgAN Model (Ready-to-Use)
Modeling Principle
This model mimics IgAN through chronic antigen stimulation and impaired hepatic IgA clearance. Repeated BSA exposure induces mucosal immune activation and increased IgA production, while LPS enhances systemic inflammation. Concurrent CCl₄-induced liver injury reduces IgA clearance, promoting formation and mesangial deposition of IgA-containing immune complexes, leading to renal injury.
Workflow
Animal Strains
BALB/c mice, Sprague-Dawley rats
Key Readouts
- 24 h urinary protein, urinary albumin
- Serum creatinine (SCr), blood urea nitrogen (BUN)
- Immunofluorescence (IgA, C3 deposition)
- Histopathology (H&E, PAS staining,etc)
Spontaneous IgAN Model (Custom Development)
Animals with a genetic predisposition (ddY or HIGA mice) produce high levels of aberrantly glycosylated IgA. Over time, circulating IgA-containing immune complexes slowly form and deposit within the glomerular mesangium. This results in age-dependent mesangial activation and expansion of the mesangial matrix leading to renal injury resembling chronic disease progression.
Key Readouts
- Progressive proteinuria (age-dependent increase)
- Mesangial IgA deposition (IF staining)
- Mesangial proliferation and matrix expansion (histopathology)
Humanized / Transgenic IgAN Model (Custom Development)
Humanized mice can express human IgA1 and/or CD89 allowing for the formation of human IgA immune complexes. The deposition of these immune complexes within the mesangium activates complement pathways resulting in inflammation, mesangial proliferation, and renal injury that closely resembles human IgAN disease resulting from multi-hit pathogenesis.
Key Readouts
- Gd-IgA1 levels (ELISA-based assays)
- Circulating and deposited immune complexes
- Complement activation markers (e.g., C3 deposition)
- Renal injury indicators (proteinuria, histopathology)
Model Comparison
| Model Type | Induced Model (BSA/LPS/CCl₄) | Spontaneous Model | Humanized/Transgenic Model |
| Availability | Ready-to-use | Custom | Custom |
| Disease Onset | Fast | Slow | Moderate |
| Mechanism Relevance | Moderate | Moderate | High |
| Reproducibility | High | Medium | Medium |
| Clinical Translation | Medium | Medium | High |
| Study Duration | Short-term | Long-term | Medium |
| Best For | Efficacy screening studies | Longitudinal disease progression studies | Mechanistic and translational research (human relevance) |
Study Examples
Significant IgA deposition in the glomerular mesangium
Fig. 2. IgAN induction led to significant IgA deposition in the glomeruli of IgAN model group compared to controls (Zhao J, Yang Y, et al. 2021).
Increased proteinuria and renal function impairment (SCr, BUN)
Fig. 3. The 24-hour urine protein level (b), red blood cell count (c), creatinine (d) and BUN (e) in the IgAN model group were significantly higher than those in the losartan treatment group (Xing L, Song EL, et al. 2019).
Histopathological changes such as mesangial proliferation and matrix expansion
Fig. 4. After 10 weeks, the model group showed significant renal injury, including mesangial cell proliferation, matrix expansion, tubular epithelial damage, and inflammatory cell infiltration, compared with the control group (Xing L, Song EL, et al. 2019).
Why Choose Creative Bioarray for IgA Nephropathy Models
Full-Spectrum IgAN Models
From induced models for rapid screening to spontaneous and humanized models for advanced research, we provide flexible options to match every stage of your IgA nephropathy study.
Mechanism-Based Relevance
All models are built around the multi-hit pathogenesis of IgAN, ensuring strong biological relevance for drug discovery and translational research.
End-to-End Custom Support
We offer custom study design, model development, and multi-parameter readouts, enabling reliable and publication-ready preclinical data.
FAQ
What is the most commonly used IgA nephropathy animal model?
The BSA/LPS/CCl₄-induced model is the most widely used due to its reproducibility, fast disease induction, and suitability for drug efficacy screening.
How does Induced Model (BSA/LPS/CCl₄) compare to spontaneous or humanized IgAN models?
Compared with other models:
- Induced model → best for fast screening and reproducibility
- Spontaneous model → better for natural disease progression
- Humanized model → best for mechanistic and translational studies
What is the severity level of the induced IgAN model?
The BSA/LPS/CCl₄ model typically induces a moderate and controllable disease phenotype, allowing adjustment of severity through dosing frequency and duration. This makes it suitable for both screening and dose-response studies.
Can IgAN animal models be used for PK/PD studies?
Yes. The induced IgAN model can be integrated with:
- PK/PD profiling for drug exposure and response correlation
- Preliminary toxicity assessment, especially renal safety evaluation
- However, complex chronic toxicity studies may require additional model optimization.
How reproducible is the IgA nephropathy animal model?
Under standardized conditions, the induced IgAN model has a high and reproducible success rate, with consistent development of:
- Proteinuria
- IgA deposition in glomeruli
- Histopathological kidney changes
CTA – Start Your IgAN Study
Partner with Creative Bioarray to accelerate your kidney disease drug development with validated IgAN animal models and expert support.
Request a quote or discuss your study design with our scientists.
References
- Lai K. Pathogenesis of IgA nephropathy. Nat Rev Nephrol. 2012. 8, 275–283
- Zhao J, Yang Y, et al. The Clinical Significance and Potential Role of Cathepsin S in IgA Nephropathy. Front Pediatr. 2021. 9:631473.
- Xing L, Song EL, et al. Nephroprotective effect of losartan in IgA model rat. J Int Med Res. 2019. 47(10):5205-5215.