Rapid development of glomerular injury and renal failure in mice lacking p53R2.

摘要: The Rrm2b gene encodes p53R2, a catalytic subunit of ribonucleotide reductase that is required for DNA repair. Embryonic stem (ES) cells containing retroviral insertion in the locus were used to generate mutant mice. Analysis kidney RNA from (-/-) mice showed disrupted expression transcripts. pups represented at expected Mendelian ratios 10-12 days age and grew normally past weaning. Mice failed thrive after 6 weeks began die by 8 age. Phenotyping revealed died severe glomerular lesion led nephrotic syndrome chronic renal failure. In kidneys mice, podocytes enlarged there was evidence foot process effacement By age, progressive podocyte hypertrophy loss processes accompanied capillary endothelial extensive enough restrict blood flow. Collapsing glomerulopathy with avascular glomeruli widespread surviving beyond 9 Additional abnormalities other organ systems minor or consistent secondary effects These findings suggest lack protein encoded Rrm2b, has early relatively selective detrimental on glomerulus lead rapid death