Cystinuria: animal models of disease

Cystinuria is a hereditary nephropathy caused by defects in the SLC3A1 and SLC7A9 genes, which encode the subunits of the heterodimeric transporter rBAT–b^0,+AT. This complex mediates cystine reabsorption in the proximal renal tubules. Consequently, dysfunction of this complex leads to cystine accumulation in urine and the formation of cystine stones. A major challenge in patient management still remains delayed diagnosis, typically after the manifestation of urolithiasis, which particularly underscores the need to develop preventive and molecularly oriented approaches. The absence of effective therapies capable of modifying the course of the disease thus highlights the relevance of establishing adequate experimental models. Animal models—primarily murine—are clearly indispensable tools for both dissecting the molecular basis of cystinuria and for preclinical evaluation of potential novel therapeutic strategies. This comprehensive review summarizes all current data on animal models of cystinuria, with emphasis on their ability to reproduce important key aspects of the disease associated with dysfunction of the rBAT–b^0,+AT transport complex.