Cystinuria: a genetic and molecular view. What is known about animal models and cells.

IF 2.3 4区 医学 Q2 PERIPHERAL VASCULAR DISEASE
Iris Iuliano, Anna Iervolino, Yoko Suzumoto, Abbas Shams, Consiglia Longobardi, Giovambattista Capasso, Alessandra F Perna, Giovanna Capolongo
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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.

胱氨酸尿症:遗传和分子的观点。我们对动物模型和细胞的了解。
背景:胱氨酸尿症是一种罕见的遗传性小管病,由编码顶膜rBAT/b0,+AT转运体的SLC7A9和SLC3A1基因突变引起。胱氨酸尿症的全球平均发病率估计为1:7000,在患病率方面存在显著的民族地理差异。胱氨酸在尿液中积聚是由于转运蛋白缺失,这可能导致胱氨酸晶体形成甚至结石。治疗中必须使用几种策略来阻止结石的生长或产生。虽然预后良好,但很少因患者依从性差、结石复发和后续干预而导致肾功能不全。总结:已发现的与该基因型相关的所有基因突变均已报道,但该疾病表型的许多方面尚不清楚,需要进一步阐明。从生理和病理两方面阐述了rBAT/b0,+AT的分子机制。它在胱氨酸尿中的功能障碍导致胱氨酸的积累和随后的结石形成,这是通过涉及结石发展的步骤详细说明的。使用不同细胞系的体外研究能够确定产生胱氨酸尿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已经创建了不同的胱氨酸尿模型,包括A型,B型和AB型,以找到制造与人类胱氨酸尿非常相似的模型的最佳方法。关键信息:为了揭示疾病进展和潜在的治疗方法,我们概述并仔细检查了胱氨酸尿症的一些动物和细胞模型。
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来源期刊
Kidney & blood pressure research
Kidney & blood pressure research 医学-泌尿学与肾脏学
CiteScore
4.80
自引率
3.60%
发文量
61
审稿时长
6-12 weeks
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.
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