Generation and characterization of a novel rat model of primary hyperoxaluria type 1 with a nonsense mutation in alanine-glyoxylate aminotransferase gene
Yueyan Li, Rui Zheng, Guofeng Xu, Yunteng Huang, Yongmei Li, Dali Li, Hongquan Geng
Abstract
Primary hyperoxaluria type 1 is a severe inherited disorder that results in recurrent urolithiasis and renal failure. We generated an alanine-glyoxylate aminotransferase ( Agxt) Q84X nonsense mutant rat model that displayed an early onset of hyperoxaluria, spontaneous renal CaOx precipitation, bladder stone, and kidney injuries. Our results suggest an interaction of renal CaOx crystals with the activation of inflammation-, fibrosis-, and necroptosis-related pathways. In all, the Agxt Q84X rat strain has broad applicability in mechanistic studies and the development of innovative therapeutics.
Topics & Concepts
Primary hyperoxaluriaNonsense mutationGlyoxylate cycleMutantAlanineKidneyMutationMedicineBiologyGeneInternal medicineGeneticsAmino acidBiochemistryMissense mutationEnzymeKidney Stones and Urolithiasis TreatmentsPorphyrin Metabolism and DisordersBiomedical Research and Pathophysiology