The effects of the inactivation of Hydroxyproline dehydrogenase on urinary oxalate and glycolate excretion in mouse models of primary hyperoxaluria

We describe the phenotype of the Prodh2 knock out mouse model and show that the lack of HYPDH in PH mouse models results in lower levels of urinary oxalate excretion, consistent with our previous metabolic tracer and siRNA-based knockdown studies. The double knockout mouse, Grhpr KO (PH2 model) and Prodh2 KO, prevented calcium-oxalate crystal deposition in the kidney, when placed on a 1% Hyp diet. These observations support the use of the Grhpr KO mice to screen HYPDH inhibitors in vivo. Altogether these data support HYPDH as an attractive therapeutic target for PH2 and PH3 patients.Graphical abstract
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research