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Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Differences in susceptibility to develop parameters of diabetic nephropathy in four mouse strains with type 1
Stephanie Franzén1, Malou Friederich-Persson2, Angelica Fasching2
1Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden; stephanie.franzen@liu.se.
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.
Insights
Diabetic nephropathy research requires suitable animal models. This study found BALB/c mice are best for studying kidney damage progression, while C57Bl/6 and NMRI mice are useful for investigating hyperfiltration mechanisms.
Area of Science:
- Nephrology
- Diabetology
- Animal Models
Background:
- Diabetic nephropathy affects one-third of diabetes mellitus patients.
- Underlying mechanisms of diabetic nephropathy remain largely unknown.
- Developing accurate animal models is crucial for understanding disease progression.
Purpose of the Study:
- To evaluate the suitability of four common mouse strains (C57Bl/6, NMRI, BALB/c, 129Sv) for modeling diabetic nephropathy.
- To determine which strain best replicates key features of human diabetic kidney disease.
Main Methods:
- Type 1 diabetes was induced using alloxan in the four selected mouse strains.
- Glomerular filtration rate, proteinuria, and oxidative stress were measured over 10 weeks.
- Histological analysis using periodic acid-Schiff staining assessed glomerular damage.
Main Results:
- C57Bl/6 and NMRI mice showed hyperfiltration; NMRI also developed proteinuria and oxidative stress without damage.
- BALB/c mice exhibited proteinuria, oxidative stress, and glomerular damage, but no hyperfiltration.
- 129Sv mice showed proteinuria and oxidative stress, but no hyperfiltration or damage.
- All strains demonstrated a correlation between oxidative stress and proteinuria.
Conclusions:
- C57Bl/6 and NMRI mice are suitable for studying hyperfiltration mechanisms in diabetic nephropathy.
- BALB/c mice are appropriate for investigating the roles of proteinuria and histological damage in disease progression.
- 129Sv mice showed limited utility for modeling key aspects of diabetic nephropathy.

