Cystinuria: A Genetic and Molecular View – What Is Known about Animal Models and Cells

Background: Cystinuria is a rare genetic tubulopathy caused by mutations on SLC7A9 and SLC3A1 genes encoding for the apical membrane rBAT/b0,+AT transporter. The mean worldwide frequency of cystinuria is estimated to be 1:7,000 with significant ethnogeographic variation in prevalence. Cystine builds up in the urine as a result of the transporter deficit, which can cause cystine crystals to form or even stones. Several strategies must be used in treatment to stop the growth or creation of stones. Although the prognosis is favourable, renal insufficiency can very rarely be brought on by poor patient compliance, stone formation recurrence, and subsequent interventions. Summary: All the identified mutations of these genes to be responsible for the genotype have been reported, and many aspects of the disease phenotype are yet unclear and need to be elucidated. The molecular mechanism of the rBAT/b0,+AT is described under both physiological and pathological conditions. Its dysfunction in cystinuria leads to the accumulation of cystine and subsequent stone formation, which is detailed through the steps involved in stone development. In vitro studies using different cell lines enable to identify potential methodologies for generating cellular models of cystinuria and to assess therapeutic approaches. In vivo studies done on mice and rats have created different models of cystinuria, including types A, B, and AB, to find the best way to make a model that closely resembles human cystinuria. Key Message: To turn the light on the disease progression and potential treatments, we outlined and carefully examined some of the animal and cellular models of cystinuria.