Laboratory of Laboratory Animal Science and Medicine, School of Veterinary Medicine, Kitasato University, Towada, 034-8628, Japan.
Urolithiasis. 2022 Dec;50(6):679-684. doi: 10.1007/s00240-022-01356-9. Epub 2022 Aug 21.
Cystinuria is an autosomal metabolic disorder caused by mutations in the SLC3A1 and SLC7A9 genes, encoding the amino acid transporter proteins rBAT and bAT, respectively. Based on the causative gene, cystinuria is classified into 3 types: type A (SLC3A1), type B (SLC7A9), and type AB (SLC3A1 and SLC7A9). Patients with cystinuria exhibit hyperexcretion of cystine and dibasic amino acids in the urine and develop cystine crystals due to its low solubility in the urine, often resulting in calculus formation. In this study, we present an inbred strain FVB/NJcl mice affected with cystinuria. In the affected mouse kidney, Slc7a9 expression was completely abolished because of a large sequence deletion in the promoter region of the Slc7a9 mutant allele. Slc7a9-deficient mice with FVB/NJcl genetic background developed cystine calculi in the bladder with high penetrance, as compared to the previously reported mouse models of cystinuria. This model may be useful to understand the determinants of crystal aggregation, affecting calculus formation.
胱氨酸尿症是一种常染色体代谢紊乱疾病，由 SLC3A1 和 SLC7A9 基因突变引起，分别编码氨基酸转运蛋白 rBAT 和 bAT。根据致病基因，胱氨酸尿症分为 3 种类型：A型（SLC3A1）、B 型（SLC7A9）和 AB 型（SLC3A1 和 SLC7A9）。胱氨酸尿症患者尿液中胱氨酸和二碱基氨基酸排泄过多，由于其在尿液中的溶解度低，会形成胱氨酸晶体，常导致结石形成。在本研究中，我们介绍了一种患有胱氨酸尿症的近交系 FVB/NJcl 小鼠。在受影响的小鼠肾脏中，由于 Slc7a9 突变等位基因启动子区域的大片段缺失，Slc7a9 的表达完全被消除。与先前报道的胱氨酸尿症小鼠模型相比，具有 FVB/NJcl 遗传背景的 Slc7a9 缺陷型小鼠在膀胱中形成胱氨酸结石的发生率很高。该模型可能有助于理解影响结石形成的晶体聚集决定因素。
