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Course of renal injury in the Mpv17-deficient transgenic mouse
Thomas O'Bryan1, Hans Weiher2, Helmut G Rennke3
1Renal Division, University of Minnesota, Minneapolis Minnesota.
Abstract:
The mutant Mpv17 mouse is a transgenic strain that fails to express a protein that is normally expressed in the kidney and that is associated with peroxisomes. The present studies provide a quantitative examination of renal function and structure in this strain compared to its control CFW strain. By 52 wk of age, the mutant strain developed proteinuria (urinary protein to creatinine ratio: 25 +/- 14 versus 3 +/- 1, mutant versus control), albuminuria (urinary albumin to creatinine ratio: 23 +/- 15 versus 0.1 +/- 0.1, mutant versus control), and hypoalbuminemia (2.1 +/- 0.4 versus 2.5 +/- 0.2 G/dl, mutant versus control), but without arterial hypertension or major reduction in filtration (serum creatinine 0.14 +/- 0.04 versus 0.18 +/- 0.12 mg/dl, mutant versus control). The Mpv17 glomeruli were enlarged (0.98 +/- 0.12 versus 0.52 +/- 0.02 micrometer(3) x 10(6), mutant versus control). Glomerular sclerosis became widespread (95 +/- 3 versus 23 +/- 32%, mutant versus control) and was preceded by mesangiolysis and microaneurysms. Tubulointerstitial disease was conspicuous by its absence. The intrarenal vasculature was normal in the mutant mice. Electron microscopy demonstrated focal foot process fusion and mesangiolysis. Thus, this mutant strain of mouse develops proteinuria and a distinct glomerulopathy including mesangiolysis but little interstitial injury all due to the loss of expression of a single gene.
Insights
Mice lacking the Mpv17 protein develop kidney disease characterized by proteinuria, albuminuria, and enlarged glomeruli with sclerosis. This distinct glomerulopathy results from the loss of a single gene
Area of Science:
- Nephrology
- Genetics
- Molecular Biology
Background:
- The Mpv17 mouse model lacks a peroxisome-associated kidney protein.
- Understanding the consequences of this genetic deficiency is crucial for renal research.
Purpose of the Study:
- To quantitatively assess renal function and structure in Mpv17 mutant mice compared to controls.
- To elucidate the specific pathological changes leading to kidney dysfunction in this model.
Main Methods:
- Comparative analysis of renal function markers (proteinuria, albuminuria, serum creatinine) between mutant and control mice.
- Histological and electron microscopy examination of kidney tissue to evaluate glomerular and tubulointerstitial structures.
- Quantitative assessment of glomerular size and sclerosis prevalence.
Main Results:
- Mutant mice exhibited significant proteinuria, albuminuria, and hypoalbuminemia by 52 weeks.
- Glomeruli were enlarged in Mpv17 mice, with widespread glomerular sclerosis, mesangiolysis, and microaneurysms.
- No significant arterial hypertension or reduction in glomerular filtration rate was observed; tubulointerstitial disease was minimal.
Conclusions:
- Loss of the Mpv17 gene results in a unique glomerulopathy characterized by mesangiolysis and sclerosis, leading to proteinuria.
- The Mpv17 mouse model provides a valuable tool for studying the genetic basis of proteinuric kidney diseases.
- Despite severe glomerular injury, the absence of significant tubulointerstitial disease highlights a specific pathogenic pathway.