Iris Iuliano, Anna Iervolino, Yoko Suzumoto, Abbas Shams, Consiglia Longobardi, Giovambattista Capasso, Alessandra F Perna, Giovanna Capolongo
{"title":"Cystinuria: a genetic and molecular view. What is known about animal models and cells.","authors":"Iris Iuliano, Anna Iervolino, Yoko Suzumoto, Abbas Shams, Consiglia Longobardi, Giovambattista Capasso, Alessandra F Perna, Giovanna Capolongo","doi":"10.1159/000547038","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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 1:7000 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 favorable, renal insufficiency can very rarely be brought on by poor patient compliance, stone formation recurrence and subsequent interventions.</p><p><strong>Summary: </strong>All the identified mutations of these genes to be responsible for the genotype have been reported, 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.</p><p><strong>Key message: </strong>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.</p>","PeriodicalId":17813,"journal":{"name":"Kidney & blood pressure research","volume":" ","pages":"1-16"},"PeriodicalIF":2.3000,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Kidney & blood pressure research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000547038","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}
引用次数: 0
Abstract
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 1:7000 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 favorable, 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, 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.
期刊介绍:
This journal comprises both clinical and basic studies at the interface of nephrology, hypertension and cardiovascular research. The topics to be covered include the structural organization and biochemistry of the normal and diseased kidney, the molecular biology of transporters, the physiology and pathophysiology of glomerular filtration and tubular transport, endothelial and vascular smooth muscle cell function and blood pressure control, as well as water, electrolyte and mineral metabolism. Also discussed are the (patho)physiology and (patho) biochemistry of renal hormones, the molecular biology, genetics and clinical course of renal disease and hypertension, the renal elimination, action and clinical use of drugs, as well as dialysis and transplantation. Featuring peer-reviewed original papers, editorials translating basic science into patient-oriented research and disease, in depth reviews, and regular special topic sections, ''Kidney & Blood Pressure Research'' is an important source of information for researchers in nephrology and cardiovascular medicine.