title: Course of renal injury in the Mpv17-deficient transgenic mouse.
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.
authors.affiliation: Renal Division, University of Minnesota, Minneapolis Minnesota.
authors.forename: Thomas
authors.initials: T
authors.lastname: O'Bryan
authors.affiliation: Institut für Diabetes Forschung, Munich, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Weiher
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Helmut G
authors.initials: HG
authors.lastname: Rennke
authors.affiliation: Renal Division, University of Minnesota, Minneapolis Minnesota.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kren
authors.affiliation: Renal Division, University of Minnesota, Minneapolis Minnesota.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Hostetter
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D004195:Disease Models, Animal; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics* / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D011507:Proteinuria / Q000235:genetics