Humanized CD89-hIGHA1 Mouse Model of Spontaneous lgA Nephropathy

This poster introduces the B6-Cd14-hCD89/hIGHA1 dual-humanized mouse model, which spontaneously recapitulates human IgA nephropathy features, including glomerular human IgA deposition, persistent proteinuria, progressive renal histopathology (mesangial proliferation, matrix expansion, inflammation), and functional decline. Pharmacological validation with Telitacicept demonstrates translational utility for therapeutic evaluation and mechanistic studies.

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Humanized CD89-hIGHA1 Mouse Model of Spontaneous lgA Nephropathy

Unlocking Spontaneous IgAN Pathology with a Dual-Humanized Platform

Clinically Relevant Spontaneous Pathogenesis

Unlike conventional induced models, this dual-humanized strain (expressing both human CD89 on myeloid cells and human IgA1) spontaneously develops hallmark IgAN features without exogenous triggers, including progressive glomerular human IgA deposition, persistent proteinuria from early age, elevated BUN, and age-dependent histopathological lesions (mesangial hypercellularity, matrix expansion, inflammatory infiltration, protein casts).

Precise Humanized Genetic Engineering

Detailed knock-in strategies are provided: human IGHA1 integrated into the mouse immunoglobulin heavy-chain locus for human IgA1 expression, and human CD89 coding sequence inserted into the mouse Cd14 locus under the endogenous promoter, ensuring myeloid-lineage-restricted expression that mirrors human FcαRI biology.

Comprehensive Longitudinal Phenotypic Characterization

Includes time-course data on urinary protein excretion, serum BUN levels, immunofluorescence quantification of glomerular IgA deposition across sexes and ages (27, 31, and 36 weeks), and progressive histopathological scoring, enabling robust baseline reference for study design.

Pharmacological Validation with Clinically Relevant Agent

Demonstrates therapeutic response to Telitacicept (TACI-Fc fusion protein targeting BAFF/APRIL), with significant reduction in circulating human IgA levels and corresponding attenuation of glomerular IgA deposition, confirming the model's predictive validity for immunomodulatory interventions.

Translational Applications for Drug Development

The model is suitable for efficacy evaluation of B-cell/plasma cell-targeted therapies, complement inhibitors, anti-inflammatory agents, and renoprotective compounds, supporting mechanistic exploration and IND-enabling preclinical studies in IgAN.

Download the full poster to access detailed genetic strategies, validation data, pharmacological proof-of-concept, and experimental protocols. Advance your IgAN therapeutic program with Ace Therapeutics' clinically relevant spontaneous model platform.

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