https://doi.org/10.1007/s00392-025-02625-4
1Universitätsmedizin Mannheim der Universität Heidelberg Experimentelle Pharmakologie Mannheim, Deutschland; 2Universitätsmedizin Mannheim der Universität Heidelberg Institut für Herz-Kreislaufforschung Mannheim, Deutschland
Aim: Streptozotocin (STZ)-induced diabetic mice are commonly employed for studying diabetic complications. Body weight, as well as tibia length, has been used to standardize organ weight. The aim of the present study is to assess the reliability of various normalization methods for organ weight in STZ-induced diabetes across two substrains of C57BL6 background mice.
Methods: To establish type 1 diabetic models, C57BL6/N (6N) and C57BL6/J (6J) wild-type mice were administered STZ via intraperitoneal injection. Blood glucose (BG) levels and body weight (BW) were regularly monitored. After 1, 3 and 6 months post diabetes induction, HbA1c levels, tibia length (TL) and weights of the heart (HW), kidney (KW) and bladder (BLW) were measured. Organ weights were standardized by BW, TL and cubic TL (TL3). Correlations between organ weights and BW, TL and TL3 were assessed to evaluate diabetes-related organ hypertrophy.
Results: Comparing to the 6J mice, 6N mice exhibited a faster peak time of BG levels, indicating higher sensitivity to STZ induction. In all diabetic mice, BW decreased significantly within the first week before stabilizing, suggesting that BW may be an unreliable parameter for organ weights standardization. Both 6N and 6J diabetic mice exhibited decreased HW/TL and HW/TL3 ratios at one-month post-diabetes induction, indicating the reduction in heart size. Conversely, the BLW/TL and BLW/TL3 ratios significantly increased in 6J diabetic mice but not in 6N, suggesting that the 6J substrain could be more suitable for early-stage studies of diabetic bladder complications, particularly at the early stages of the disease. At 3 months post-diabetes induction, the ratios of KW to TL and TL3 were significantly increased in 6J diabetic mice, suggesting that the 6J mice could be a better choice for early-stage diabetic nephropathy researches. At 6 months, nearly all organs in diabetic mice exhibited significant measurement differences compared to non-diabetic controls, indicating that both 6N and 6J mice are suitable models for investigating long-term diabetic complications.
Conclusion: Compared to 6N substrain, 6J mice may serve as a more effective murine model for studying early-stage diabetic complication in heart, kidney and bladder. For reliable standardization, TL and TL3 appear to be more advantageous metrics than BW, especially in diabetic mice experiencing considerable body weight loss.