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Are insights gained from NOD mice sufficient to guide clinical translation? Another inconvenient truth
1Department of Immunohaematology and Blood Transfusion, E3-Q, LUMC, P.O. Box 9600, NL-2300 RC Leiden, the Netherlands. boroep@lumc.nl
Abstract:
Despite decades of research using various animal models for type 1 diabetes, we are still struggling to define the initiating autoantigens, the precise mechanisms of beta cell destruction, and suitable immune-based interventions to prevent or treat human diabetes. Animal models, such as the non-obese diabetic (NOD) mouse and the biobreeding (BB) rat, develop immune-mediated diseases with features resembling type 1 diabetes in humans. Although these animal models of autoimmune diabetes have proved to be valuable tools to study certain aspects of the disease process, they have also led to misconceptions and erroneous extrapolations, as well as false expectations with regard to the efficacy of immunotherapy. It is therefore time to ask ourselves whether we are making major strategic mistakes when employing rodent models for the study of type 1 diabetes. This review will describe where rodent models have provided us with proper guidance and where they have misled us, concluding that each model only offers partial information with undefined clinical value. Therefore, a more critical attitude and repetition of crucial observations in different model settings will be necessary in the future. I will argue that animal models have limited but evident value when it comes to teaching us about type 1 diabetes in humans, and we can take advantage of this value more efficiently.
Insights
Animal models for type 1 diabetes offer limited insights due to species differences. A critical re-evaluation is needed to better understand human autoimmune diabetes and improve immunotherapy strategies.
Area of Science:
- Immunology
- Endocrinology
- Diabetology
Background:
- Type 1 diabetes research faces challenges in identifying autoantigens and understanding beta cell destruction mechanisms.
- Existing animal models, like NOD mice and BB rats, mimic aspects of human autoimmune diabetes but have limitations.
Purpose of the Study:
- To critically assess the utility and limitations of rodent models in type 1 diabetes research.
- To identify areas where animal models have provided accurate guidance and where they have led to misconceptions.
- To propose a more effective approach for utilizing animal model data in human type 1 diabetes studies.
Main Methods:
- Review and critical analysis of existing literature on animal models for type 1 diabetes.
- Comparison of findings from different rodent models (e.g., NOD mouse, BB rat) with human type 1 diabetes.
- Evaluation of the impact of animal models on the development of immunotherapies.
Main Results:
- Rodent models have provided valuable, yet partial, information about autoimmune diabetes.
- These models have also contributed to misconceptions and unrealistic expectations regarding immunotherapy efficacy.
- Each model offers incomplete data with uncertain clinical relevance for human type 1 diabetes.
Conclusions:
- A more critical and rigorous approach is necessary when interpreting data from animal models.
- Replication of key findings across different model systems is crucial for validation.
- Animal models have limited but demonstrable value for understanding human type 1 diabetes, requiring more efficient utilization.
