In vivo Drosophilia genetic model for calcium oxalate nephrolithiasis

Hirata, T., Cabrero, P. , Berkholz, D.S., Bondeson, D.P., Ritman, E.L., Thompson, J.R., Dow, J.A.T. and Romero, M.F. (2012) In vivo Drosophilia genetic model for calcium oxalate nephrolithiasis. American Journal of Physiology: Renal Physiology, 303(11), F1555-F1562. (doi: 10.1152/ajprenal.00074.2012)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cabrero, Mr Pablo and Dow, Professor Julian
• Authors: Hirata, T., Cabrero, P., Berkholz, D.S., Bondeson, D.P., Ritman, E.L., Thompson, J.R., Dow, J.A.T., and Romero, M.F.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: American Journal of Physiology: Renal Physiology
• Publisher: American Physiological Society
• ISSN: 1931-857X
• ISSN (Online): 1522-1466
• Published Online: 19 September 2012