title: In vivo Drosophilia genetic model for calcium oxalate nephrolithiasis.
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.
authors.affiliation: Dept. Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Taku
authors.initials: T
authors.lastname: Hirata
authors.forename: Pablo
authors.initials: P
authors.lastname: Cabrero
authors.forename: Donald S
authors.initials: DS
authors.lastname: Berkholz
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Bondeson
authors.forename: Erik L
authors.initials: EL
authors.lastname: Ritman
authors.forename: James R
authors.initials: JR
authors.lastname: Thompson
authors.forename: Julian A T
authors.initials: JA
authors.lastname: Dow
authors.forename: Michael F
authors.initials: MF
authors.lastname: Romero
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D027321:Anion Transport Proteins / Q000235:genetics / Q000378:metabolism; D002129:Calcium Oxalate / Q000378:metabolism; D004330:Drosophila / Q000235:genetics*; D055785:Gene Knockdown Techniques; D007684:Kidney Tubules / Q000378:metabolism; D023421:Models, Animal; D008957:Models, Genetic; D053040:Nephrolithiasis / Q000235:genetics* / Q000378:metabolism
chemical_list: D027321:Anion Transport Proteins; D002129:Calcium Oxalate