Course of renal injury in the Mpv17-deficient transgenic mouse

The mutant Mpv 17 mouse is a transgenic strain that fails to express a prot ein that is normally expressed in the kidney and that is associated with pe roxisomes. The present studies provide a quantitative examination of renal function and structure in this strain compared to its control CFW strain. B y 52 wk of age, the mutant strain developed proteinuria (urinary protein to creatinine ratio: 25 +/- 14 versus 3 +/- 1, mutant versus control), albumi nuria (urinary albumin to creatinine ratio: 23 +/- 15 versus 0.1 +/- 0.1, m utant versus control), and hypoalbuminemia (2.1 +/- 0.4 versus 2.5 +/- 0.2 G/dl, mutant versus control), but without arterial hypertension or major re duction in filtration (serum creatinine 0.14 +/- 0.04 versus 0.18 +/- 0.12 mg/dl, mutant versus control). The Mpv 17 glomeruli were enlarged (0.98 +/- 0.12 versus 0.52 +/- 0.02 mu m(3) x 10(6), mutant versus control). Glomeru lar sclerosis became widespread (95 +/- 3 versus 23 +/- 32%, mutant versus control) and was preceded by mesangiolysis and microaneurysms. Tubulointers titial disease was conspicuous by its absence. The intrarenal vasculature w as normal in the mutant mice. Electron microscopy demonstrated focal foot p rocess fusion and mesangiolysis, Thus, this mutant strain of mouse develops proteinuria and a distinct glomerulopathy including mesangiolysis but litt le interstitial injury all due to the loss of expression of a single gene.