01-10-2004 | For Debate
Animal models have little to teach us about Type 1 diabetes: 2. In opposition to this proposal
Published in: Diabetologia | Issue 10/2004
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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.
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
|
+
|
+
|
+
|