title: Differences in susceptibility to develop parameters of diabetic nephropathy in four mouse strains with type 1 diabetes.
abstract: One-third of diabetes mellitus patients develop diabetic nephropathy, and with underlying mechanisms unknown it is imperative that diabetic animal models resemble human disease. The present study investigated the susceptibility to develop diabetic nephropathy in four commonly used and commercially available mouse strains with type 1 diabetes to determine the suitability of each strain. Type 1 diabetes was induced in C57Bl/6, NMRI, BALB/c, and 129Sv mice by alloxan, and conscious glomerular filtration rate, proteinuria, and oxidative stress levels were measured in control and diabetic animals at baseline and after 5 and 10 wk. Histological alterations were analyzed using periodic acid-Schiff staining. Diabetic C57Bl/6 displayed increased glomerular filtration rate, i.e., hyperfiltration, whereas all other parameters remained unchanged. Diabetic NMRI developed the most pronounced hyperfiltration as well as increased oxidative stress and proteinuria but without glomerular damage. Diabetic BALB/c did not develop hyperfiltration but presented with pronounced proteinuria, increased oxidative stress, and glomerular damage. Diabetic 129Sv displayed proteinuria and increased oxidative stress without glomerular hyperfiltration or damage. However, all strains displayed intrastrain correlation between oxidative stress and proteinuria. In conclusion, diabetic C57Bl/6 and NMRI both developed glomerular hyperfiltration but neither presented with histological damage, although NMRI developed low-degree proteinuria. Thus these strains may be suitable when investigating the mechanism causing hyperfiltration. Neither BALB/c nor 129Sv developed hyperfiltration although both developed pronounced proteinuria. However, only BALB/c developed detectable histological damage. Thus BALB/c may be suitable when studying the roles of proteinuria and histological alterations for the progression of diabetic nephropathy.
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden; stephanie.franzen@liu.se.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Franzén
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden; and.
authors.forename: Malou
authors.initials: M
authors.lastname: Friederich-Persson
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden; and.
authors.forename: Angelica
authors.initials: A
authors.lastname: Fasching
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden; and.
authors.forename: Peter
authors.initials: P
authors.lastname: Hansell
authors.affiliation: Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan.
authors.forename: Masaomi
authors.initials: M
authors.lastname: Nangaku
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden; Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden; and.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Palm
mesh_terms: D000496:Alloxan / Q000009:adverse effects; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications*; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000150:complications*; D003928:Diabetic Nephropathies / Q000453:epidemiology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000453:epidemiology* / Q000503:physiopathology*; D005919:Glomerular Filtration Rate / Q000502:physiology; D015994:Incidence; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018384:Oxidative Stress / Q000502:physiology; D011507:Proteinuria / Q000453:epidemiology / Q000503:physiopathology; D012307:Risk Factors; D013045:Species Specificity
chemical_list: D000496:Alloxan
keywords: 129Sv; BALB/c; C57Bl/6; NMRI; diabetic nephropathy; kidney function