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Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Rodent models of diabetic nephropathy: their utility and limitations
Munehiro Kitada1, Yoshio Ogura2, Daisuke Koya1
1Division of Anticipatory Molecular Food Science and Technology, Medical Research Institute; Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
Abstract:
Diabetic nephropathy is the most common cause of end-stage renal disease. Therefore, novel therapies for the suppression of diabetic nephropathy must be developed. Rodent models are useful for elucidating the pathogenesis of diseases and testing novel therapies, and many type 1 and type 2 diabetic rodent models have been established for the study of diabetes and diabetic complications. Streptozotocin (STZ)-induced diabetic animals are widely used as a model of type 1 diabetes. Akita diabetic mice that have an Ins2+/C96Y mutation and OVE26 mice that overexpress calmodulin in pancreatic β-cells serve as a genetic model of type 1 diabetes. In addition, db/db mice, KK-Ay mice, Zucker diabetic fatty rats, Wistar fatty rats, Otsuka Long-Evans Tokushima Fatty rats and Goto-Kakizaki rats serve as rodent models of type 2 diabetes. An animal model of diabetic nephropathy should exhibit progressive albuminuria and a decrease in renal function, as well as the characteristic histological changes in the glomeruli and the tubulointerstitial lesions that are observed in cases of human diabetic nephropathy. A rodent model that strongly exhibits all these features of human diabetic nephropathy has not yet been developed. However, the currently available rodent models of diabetes can be useful in the study of diabetic nephropathy by increasing our understanding of the features of each diabetic rodent model. Furthermore, the genetic background and strain of each mouse model result in differences in susceptibility to diabetic nephropathy with albuminuria and the development of glomerular and tubulointerstitial lesions. Therefore, the validation of an animal model reproducing human diabetic nephropathy will significantly facilitate our understanding of the underlying genetic mechanisms that contribute to the development of diabetic nephropathy. In this review, we focus on rodent models of diabetes and discuss the utility and limitations of these models for the study of diabetic nephropathy.
Insights
Diabetic nephropathy, a leading cause of kidney failure, requires new treatments. This review examines rodent models for studying diabetic nephropathy, highlighting their utility and limitations in understanding disease mechanisms.
Area of Science:
- Nephrology
- Endocrinology
- Animal Models
Background:
- Diabetic nephropathy is the primary cause of end-stage renal disease, necessitating the development of novel therapeutic strategies.
- Rodent models are crucial for investigating disease pathogenesis and evaluating potential treatments for diabetes and its complications.
Approach:
- This review analyzes various rodent models of type 1 and type 2 diabetes, including streptozotocin-induced, Akita, OVE26, db/db, KK-Ay, Zucker diabetic fatty, Wistar fatty, Otsuka Long-Evans Tokushima Fatty, and Goto-Kakizaki rats.
- The suitability of these models for studying diabetic nephropathy is assessed based on their ability to replicate key features such as albuminuria, decreased renal function, and characteristic histological changes.
Key Points:
- Currently, no single rodent model perfectly recapitulates all aspects of human diabetic nephropathy.
- Differences in genetic background and strain influence susceptibility to albuminuria and renal lesions in diabetic models.
- Available models offer valuable insights into disease mechanisms, despite their limitations.
Conclusions:
- Further validation of animal models that accurately mimic human diabetic nephropathy is essential for advancing our understanding of the underlying genetic factors.
- Continued research using existing rodent models will contribute to the development of effective therapies for diabetic nephropathy.
