RRC ID 36017
Author Hirata T, Cabrero P, Berkholz DS, Bondeson DP, Ritman EL, Thompson JR, Dow JA, Romero MF.
Title In vivo Drosophilia genetic model for calcium oxalate nephrolithiasis.
Journal Am J Physiol Renal Physiol
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.
Volume 303(11)
Pages F1555-62
Published 2012-12-1
DOI 10.1152/ajprenal.00074.2012
PII ajprenal.00074.2012
PMID 22993075
PMC PMC3532482
MeSH Animals Animals, Genetically Modified Anion Transport Proteins / genetics Anion Transport Proteins / metabolism Calcium Oxalate / metabolism Drosophila / genetics* Gene Knockdown Techniques Kidney Tubules / metabolism Models, Animal* Models, Genetic* Nephrolithiasis / genetics* Nephrolithiasis / metabolism
IF 3.191
Times Cited 27
Drosophila 5485R-3