Allelic effects on uromodulin aggregates drive autosomal dominant tubulointerstitial kidney disease

Autosomal dominant tubulointerstitial kidney disease (ADTKD) caused by UMOD mutations is characterized by strong interfamilial variability. We generated two mutant Umod knock-in mouse models, harbouring two mutations associated with drastic differences in kidney survival in ADTKD patients. We performed bulk RNA-sequencing of kidney extracts from Umod KI mice at an early (1 month) and advanced (4 months) stage of disease. RNA-sequencing of mouse kidneys from Umod wild type and mutant mice (p.C171Y, p.R186S) at 1 and 4 months of age.