The etiology of IgA nephropathy (IgAN) remains only partly understood, but the presence of IgA antibodies together with the myeloid IgA receptor FcαRI/CD89 complexes in the circulation of patients is considered a specific pathogenic factor for mesangial deposition. The absence of a CD89 ortholog in rodents, coupled with the differences in the IgA systems between humans and mice, further hinders exploration of IgAN pathogenesis. To better understand the pathogenesis of IgAN, we developed a transgenic mouse model expressing human IgA1 and CD89 (B6-Cd14-hCD89/hIGHA1), in which CD89 is expressed under the control of an endogenous murine CD14 promoter on blood and tissue monocytes/macrophages. This results in a relevant preclinical mouse model useful for the evaluation of CD89 and IgA1-targeted therapies. The B6-Cd14-hCD89/hIGHA1 mice exhibited an IgAN-like phenotype. This novel model can contribute significantly to unraveling the mechanisms underlying IgAN and provide a clinically relevant mouse model for evaluating novel therapeutics against IgAN.