Iuliano Iris, Iervolino Anna, Suzumoto Yoko, Shams Abbas, Longobardi Consiglia, Capasso Giovambattista, Perna Alessandra F, Capolongo Giovanna
Kidney Blood Press Res. 2025 Jun 25:1-16. doi: 10.1159/000547038.
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.
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.
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.
胱氨酸尿症是一种罕见的遗传性肾小管病，由编码顶端膜rBAT/b0,+AT转运体的SLC7A9和SLC3A1基因突变引起。据估计，胱氨酸尿症在全球的平均发病率为1:7000，患病率在种族地理上存在显著差异。由于转运体缺陷，胱氨酸在尿液中积聚，这可能导致胱氨酸晶体形成甚至结石。治疗中必须采用多种策略来阻止结石的生长或形成。尽管预后良好，但患者依从性差、结石形成复发及后续干预措施极少见地会导致肾功能不全。
所有已确定的导致该基因型的这些基因的突变均已被报道，但疾病表型的许多方面仍不清楚，需要进一步阐明。rBAT/b0,+AT在生理和病理条件下的分子机制均有描述。其在胱氨酸尿症中的功能障碍导致胱氨酸积累及随后的结石形成，这通过结石形成过程中的步骤进行了详细说明。使用不同细胞系的体外研究能够确定生成胱氨酸尿症细胞模型的潜在方法，并评估治疗方法。在小鼠和大鼠身上进行的体内研究建立了不同的胱氨酸尿症模型，包括A、B和AB型，以找到构建最接近人类胱氨酸尿症模型的最佳方法。
为了揭示疾病进展和潜在治疗方法，我们概述并仔细研究了一些胱氨酸尿症的动物和细胞模型。
