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.

Deletion of Uncoupling Protein‐2 reduces renal mitochondrial leak respiration, intrarenal hypoxia and proteinuria in a mouse model of type 1 diabetes

“…UCP‐2 −/− mice (B6.129S4‐Ucp2tm1Lowl/J, stock no. 005934) and corresponding wild‐type littermates were purchased from Jackson Laboratories (Bar Harbor, ME, USA), n = 6‐11 in all groups . All animal experiments conform to the “European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes” (Council of Europe No 123, Strasbourg 1985) and were approved by the local Animal Care and Use Committee for Uppsala University.…”

“…005934) and corresponding wild-type littermates were purchased from Jackson Laboratories (Bar Harbor, ME, USA), n = 6-11 in all groups. 46…”

Endothelin type A receptor inhibition normalises intrarenal hypoxia in rats used as a model of type 1 diabetes by improving oxygen delivery

“…The urinary protein concentration was analysed according to the manufacturer's protocol (DC protein assay; Bio-Rad Laboratories, Sundbyberg, Sweden). Na + concentrations were analysed using flame photometry (model IL543; Instrumentation Lab, Milan, Italy), and the concentration of thiobarbituric acid reactive substances (TBARS) was measured as previously described [22]. Renal vascular resistance (RVR) was calculated as the MAP divided by the RBF, and QO 2 as the arteriovenous extraction of oxygen multiplied by the RBF.…”

Pronounced kidney hypoxia precedes albuminuria in type 1 diabetic mice

“…3). We previously reported a progressive increase in diabetes-induced glomerular leakage in several different mouse strains (2). An increase in urinary protein excretion was evident during week 5 to week 10 after the onset of diabetes.…”

“…On day 16 after the induction of diabetes, all mice were placed in metabolic cages to determine 24-h urinary albumin excretion (Mouse Albumin ELISA Kit; Bethyl Laboratories, Montgomery, TX) corrected for creatinine (Abbott Laboratories, Abbott Park, IL). Conscious glomerular filtration rates were determined as previously described (2).…”