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Published in: Diabetologia 10/2004

01-10-2004 | For Debate

Animal models have little to teach us about Type 1 diabetes: 2. In opposition to this proposal

Authors: E. H. Leiter, M. von Herrath

Published in: Diabetologia | Issue 10/2004

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Excerpt

The contrarians have to agree with their opponents that animal models in general, and rodent models of Type 1 diabetes in particular, are imperfect reflections of human disease [1]. This is the inevitable consequence of an evolutionary separation of over 65 million years. While pointing out the numerous differences that distinguish human from rodent immune systems, Mestas and Hughes [2] note that “after all, most of us do not live with our noses a half-inch off the ground.” Clearly, divergent evolution in genera occupying different niches argues against using a mouse or rat model of spontaneous Type 1 diabetes as an exact blueprint for disease in humans. There are, however, sufficient similarities between the aetiopathogenesis of Type 1 diabetes in humans, mice and rats to justify the efforts devoted to animal research (Table 1). While there are significant differences between the various rodent models, this heterogeneity surely carries important lessons for understanding the potential heterogeneity underlying this complex disease in humans.
Table 1
Comparison of insulin-dependent diabetes in humans, mice and rats
Characteristic
Humans
NOD mice
Lymphopenic BB diabetes-prone ratsa
Non-lymphopenic BB diabetes-resistant (inducible) ratsa
Genetic predisposition (MHC class II linkage)
+
+
+
+
Complex polygenic control
+
+
Oligogenic
Oligogenic
Environmental effects on gene penetrance
Probable
+
+
+
Disease transmissible via bone marrow
+
+
+
?
T-lymphocyte-driven insulitic lesions
+
+
+
+
Leucocytic infiltrates found in other organs
Sometimes
+
+
+
Defective peripheral immunoregulation
+
+
+
+
Humoral reactivity to beta cells
+
+
-
?
Endogenous retroviral genes expressed in beta cells
-
+
-
?
Diabetic ketoacidosis if untreated
+
Mild
+
+
Sex bias
-
+
-
-
Successful intervention therapies
In progress
+
+
+
a Thanks to J. Mordes, University of Massachusetts Medical School (Worcester, Mass., USA) for advice regarding rat phenotypes
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Metadata
Title
Animal models have little to teach us about Type 1 diabetes: 2. In opposition to this proposal
Authors
E. H. Leiter
M. von Herrath
Publication date
01-10-2004
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 10/2004
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-004-1518-0

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