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Updated: Aug 19, 2026
Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration
Published on: June 7, 2014
Rapid development of glomerular injury and renal failure in mice lacking p53R2
David R Powell1, Urvi Desai, Mary Jean Sparks
1Lexicon Genetics Incorporated, The Woodlands, TX 77381, USA. dpowell@lexgen.com
Abstract:
The Rrm2b gene encodes p53R2, a catalytic subunit of ribonucleotide reductase that is required for DNA repair. Embryonic stem (ES) cells containing a retroviral insertion in the Rrm2b locus were used to generate mutant mice. Analysis of kidney RNA from Rrm2b (-/-) mice showed that the retroviral insertion disrupted expression of Rrm2b transcripts. Rrm2b (-/-) pups were represented at the expected Mendelian ratios at 10-12 days of age and grew normally past weaning. Mice failed to thrive after 6 weeks of age and began to die by 8 weeks of age. Phenotyping revealed that Rrm2b (-/-) mice died from a severe glomerular lesion that led to nephrotic syndrome and chronic renal failure. In kidneys of Rrm2b (-/-) mice, podocytes were enlarged and there was evidence of foot process effacement by 6 weeks of age. By 8 weeks of age, progressive podocyte hypertrophy and loss of foot processes was accompanied by hypertrophy of glomerular capillary endothelial cells that was extensive enough to restrict capillary blood flow. Collapsing glomerulopathy with avascular glomeruli was widespread in mice surviving beyond 9 weeks of age. Additional abnormalities in other organ systems were minor or consistent with secondary effects of renal failure. These findings suggest that lack of p53R2, the protein encoded by Rrm2b, has early and relatively selective detrimental effects on the kidney glomerulus that lead to rapid death from progressive renal failure.
Insights
Mice lacking the Rrm2b gene, which encodes p53R2, developed severe kidney damage and died from renal failure. This highlights p53R2
Area of Science:
- Genetics and Molecular Biology
- Nephrology
- Developmental Biology
Background:
- The Rrm2b gene encodes p53R2, a crucial component of ribonucleotide reductase involved in DNA repair.
- Understanding the in vivo function of Rrm2b is essential for comprehending DNA repair mechanisms and potential therapeutic targets.
Purpose of the Study:
- To investigate the physiological role of the Rrm2b gene and its encoded protein, p53R2, in mammalian development and organ function.
- To characterize the phenotypic consequences of Rrm2b deficiency in a mouse model.
Main Methods:
- Generation of Rrm2b-deficient mice using retroviral insertion in embryonic stem cells.
- Analysis of gene expression in Rrm2b (-/-) mice.
- Detailed phenotyping of Rrm2b (-/-) mice, including histological examination of kidney tissues.
Main Results:
- Rrm2b (-/-) mice exhibited normal development until 6 weeks of age, followed by failure to thrive and mortality by 8 weeks.
- Severe glomerular lesions, including podocyte hypertrophy, foot process effacement, and glomerular capillary endothelial cell hypertrophy, were observed.
- Progressive collapsing glomerulopathy and renal failure were the primary causes of death in Rrm2b (-/-) mice.
Conclusions:
- The absence of p53R2 leads to selective and early detrimental effects on the kidney glomerulus.
- Rrm2b deficiency results in progressive renal failure and mortality, underscoring the critical role of p53R2 in maintaining glomerular integrity and kidney function.
