Normal urinary oxalate excretion in 4-hydroxy-2-oxo-glutarate aldolase 1 (HOGA1) deficient mice with AGT expression...

Primary hyperoxaluria type 3 (PH3) is caused by mutations in Hoga1 gene. PH3 individuals develop nephrolithiasis, but the mechanism underlying hyperoxaluria is unclear and a mouse model recapitulating the human disease can provide insights into the pathogenesis of PH3. Hoga1^-/- mice do not have increased urinary oxalate excretion, probably due to the murine mitochondrial alanine-glioxylate-aminotransferase (AGT) activity, which in humans is only expressed in peroxisomes. However, Hoga1^-/-/Agxt^-/- mice with AGT installed on peroxisome and not on mitochondria did not show increased urinary oxalate, suggesting that AGT expression in both cellular compartments is not an explanation for the lack of hyperoxaluria in Hoga1^-/- mice.