Mouse Models of Diabetic Neuropathy

Abstract

Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes and is associated with significant morbidity and mortality. DPN is characterized by progressive, distal-to-proximal degeneration of peripheral nerves that leads to pain, weakness, and eventual loss of sensation. The mechanisms underlying DPN pathogenesis are uncertain, and other than tight glycemic control in type 1 patients, there is no effective treatment. Mouse models of type 1 (T1DM) and type 2 diabetes (T2DM) are critical to improving our understanding of DPN pathophysiology and developing novel treatment strategies. In this review, we discuss the most widely used T1DM and T2DM mouse models for DPN research, with emphasis on the main neurologic phenotype of each model. We also discuss important considerations for selecting appropriate models for T1DM and T2DM DPN studies and describe the promise of novel emerging diabetic mouse models for DPN research. The development, characterization, and comprehensive neurologic phenotyping of clinically relevant mouse models for T1DM and T2DM will provide valuable resources for future studies examining DPN pathogenesis and novel therapeutic strategies.

New Horizons in Diabetic Neuropathy: Mechanisms, Bioenergetics, and Pain

“…With the recent advent of over 20 murine models of DN, there is a rich variety of experimental models from which to choose from for DN research beyond the STZ rat. These experimental models provide the tools for future research to more fully understand the differences between DN in T1D and T2D (Islam, 2013; O’Brien et al, 2014b; Yorek, 2016). …”

“…A TRPA1 antagonist reduced pain-related hypersensitivity following in STZ rats with DN (Wei et al, 2009), although an important caveat is that STZ itself can directly activate TRPA1 and evoke sensory axonal injury (Andersson et al, 2015). The experimental validation of TRPA1 antagonists in painful DN, therefore, awaits replication in one or more of the newer animal models, discussed earlier in this review (O’Brien et al, 2014b). …”

Animal models for diabetes: Understanding the pathogenesis and finding new treatments

“…This has been modelled in a range of hyperglycaemic animals such as streptozotocin-induced, high fat fed, NOD mice, Akita mice, Zucker diabetic fatty rats and BB rats which all have been discussed in detail in recent reviews [164,165]. It should be noted that a recent study shows that streptozotocin directly stimulates TRPA1, which could complicate the interpretation on results studying neuropathy in this model [166].…”

Effect of Moringa oleifera consumption on diabetic rats

“…Mouse is a good biological tool that allows the analyses of different tissues with little limitation on the amount of biological materials available. This animal model provide an important tool for study of the pathogenesis, prevention and treatment of diabetic complications [13]. Mouse is economical and requires simple husbandry compared to larger mammals, and there is a huge volume of literature on the physiology, behavior, and biochemistry of such rodents.…”