A Rat Model of IgA Nephropathy

NU 2019-196

INVENTORS

Jing Jin*
Xinfang Xie

SHORT DESCRIPTION

A novel rat model of IgA nephropathy (IgAN, also known as Berger's disease), enabling reproducible kidney mesangial deposits characteristic of the human disease for therapeutic and diagnostic evaluation.

BACKGROUND

IgAN, the most common glomerulonephritis worldwide, results from aberrantly glycosylated IgA1 in blood circulation that aggregates into poly-IgA complexes that deposit in kidneys, causing chronic kidney inflammation and eventually leading to end-stage renal disease requiring dialysis or transplantation. Existing animal models to study IgAN are problematic—mice and rats don't spontaneously develop IgAN, genetic mouse strains show unpredictable onset, dietary or transgenic models have inconsistent phenotypes, and approaches using patient-derived poly-IgA lack standardization and molecular characterization. The absence of robust animal models has severely hampered drug screening platforms and therapeutic development for this disease affecting millions globally.

ABSTRACT

Northwestern researchers have invented a method of inducing IgAN in a rodent using polymeric complexes of homo-oligomeric unglycosylated IgA Fc fragments. Each oligomer contains a biotin moiety enabling streptavidin-induced polymerization, which can be administered to an animal at specified dosages and schedules. Experimental data demonstrate that poly-rIgA injection produces prominent mesangial IgA deposition, mesangial hypercellularity, matrix expansion, IgG co-deposition, complement C3 activation, proteinuria, and electron-dense deposits resembling human IgAN pathology, while monomeric rIgA controls show no such effects, with deposits clearing over 14 days after cessation mimicking disease flare-up and resolution dynamics.

APPLICATIONS

Provides a standardized, reproducible animal model of IgAN for:
- Preclinical drug screening and therapeutic development
- Mechanistic studies of IgAN pathogenesis
- Diagnostic test validation and biomarker discovery

ADVANTAGES

Reproducibility and standardization through synthetic poly-IgA with molecularly defined, batch-consistent reagents.
Rapid and robust disease induction - daily injections for 12 days produces strong, long-lasting mesangial IgA deposits with characteristic IgAN pathology, while single bolus injection enables study of deposition/clearance dynamics.
Translational relevance and versatility - the model uses commonly available rats or mice (not specialized genetic strains), produces histologic features matching human IgAN biopsies, and provides multiple experimental paradigms within a single platform technology.

PUBLICATIONS