Dept. Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Am J Physiol Renal Physiol. 2012 Dec 1;303(11):F1555-62. doi: 10.1152/ajprenal.00074.2012. Epub 2012 Sep 19.
Nephrolithiasis is a major public health problem with a complex and varied etiology. Most stones are composed of calcium oxalate (CaOx), with dietary excess a risk factor. Because of complexity of mammalian system, the details of stone formation remain to be understood. Here we have developed a nephrolithiasis model using the genetic model Drosophila melanogaster, which has a simple, transparent kidney tubule. Drosophilia reliably develops CaOx stones upon dietary oxalate supplementation, and the nucleation and growth of microliths can be viewed in real time. The Slc26 anion transporter dPrestin (Slc26a5/6) is strongly expressed in Drosophilia kidney, and biophysical analysis shows that it is a potent oxalate transporter. When dPrestin is knocked down by RNAi in fly kidney, formation of microliths is reduced, identifying dPrestin as a key player in oxalate excretion. CaOx stone formation is an ancient conserved process across >400 My of divergent evolution (fly and human), and from this study we can conclude that the fly is a good genetic model of nephrolithiasis.
肾结石是一个具有复杂且多样病因的主要公共卫生问题。大多数结石由草酸钙（CaOx）组成，饮食过量是一个风险因素。由于哺乳动物系统的复杂性，结石形成的细节仍有待了解。在这里，我们使用遗传模型果蝇（Drosophila melanogaster）开发了肾结石模型，其具有简单、透明的肾小管。在饮食中补充草酸盐后，果蝇可靠地形成 CaOx 结石，并且可以实时观察微结石的成核和生长。Slc26 阴离子转运体 dPrestin（Slc26a5/6）在果蝇肾脏中强烈表达，生物物理分析表明它是一种有效的草酸盐转运体。当 dPrestin 在果蝇肾脏中通过 RNAi 敲低时，微结石的形成减少，表明 dPrestin 是草酸排泄的关键因素。CaOx 结石形成是一个跨越超过 4 亿年进化分歧（果蝇和人类）的古老保守过程，从这项研究中我们可以得出结论，果蝇是肾结石的良好遗传模型。
