Drosophila Model of Oxalate Nephrolithiasis
Researchers in the O'Brien Urology Research Center have developed a drosophila model of oxalate nephrolithiasis. This model is useful because formation of renal stones can occur in minutes in drosophila flies versus months or years in people.
Led by principal investigator Michael F. Romero, Ph.D., the project research team is using this drosophila model to test genes involved in calcium oxalate (CaOx) stone formation and to test potential therapeutics.
Using a genome-wide association study (GWAS) analysis of a canine CaOx model, research collaborators at the University of Minnesota identified a critical region of canine chromosome 37. This region contains 18 genes (orthologs on human chromosome 2), 12 of which have drosophila homologs and available RNAi lines.
Preliminary experiments demonstrated that urine crystallization inhibitors (thiosulfate and tannic acid) can interact with the oxalate transporter and inhibit CaOx crystal formation in tubule assays. The project screens larval and adult flies using gene knockdown, birefringence and microCT projection densities.
The three main aims of Dr. Romero's project are to:
- Use RNAi lines of the 12 canine homologs to determine which of these genes, when interrupted, alter CaOx crystal formation
- Screen compounds known to change CaOx supersaturation
- Investigate compound hits with more detailed analysis of dose dependence, mode of inhibition and effect on oxalate transporter biophysics