STZ induction mouse or rat ? how about NOD mouse or BB rat? Is there any method for viral induction ? which one will be closest to mimic natural b cell destruction ?
The two rodent models studied most extensively are the nonobese diabetic (NOD) mouse and the biobreeding (BB) rat . These two rodent models have helped define the autoimmune response that leads to the destruction of β cells and to provide clues into the pathogenesis of T1D. These models have noted that T1D is characterized by a T-cell-mediated immune response against islet autoantigens, that it can be transferred with autoreactive lymphocytes (i.e., T cells), and that the autoimmunity persists long after the loss of β cells, displaying recurrent autoimmunity when transplanted with syngeneic islets . Similar patterns of pathogenesis have been observed in humans, particularly with respect to recurrent autoimmunity.
In the NOD mouse, 200 therapies have been shown to prevent diabetes . However, it must be noted that NOD mice are resistant to tolerance induction even to nonislet tissues and grafts and thus, their immune systems appear to differ in many respects from that of nonautoimmune mice. In the BB rat, far fewer therapies have been shown to prevent diabetes.
Niraj,
From the three options you are contemplating, BB rat is a relatively better model of T1D. However, even that does not represent nearly all aspects of human disease.
So far regeneration of islets ß-cells after their complete autoimmune destruction has remained elusive. It will be wonderful if you devise a way to achieve it.
There are publications in literature describing various methods to induce ß-cell appearance in liver through transdifferentiation by use of certain seminal transcription factors, such as PDX1 (Sarah Ferber's work), but their practical use has remained rather questionable.
Best...
hi Niraj,
NOD mouse versus BB rat as rodent models for Human DMT1
Best ...
and the Beta Cell regeneration study paper.
Hope this will help you in your studies. Best wishes
Many models of b-cell regeneration have been developed. They differ in the mechanism by which regeneration occurs. Commonly used models include partial pancreatectomy in which b-cell regeneration occurs by replication, and duct ligation, where there is a lot of controversy, as the islets remain largely intact in that model while the acinar pancreas is totally destroyed. Selective b-cell ablation is also much studied, and the mechanism there is also controversial. I would say that there is no such thing as a "best" model, as the field as a whole is in a state of flux. My laboratory has studied combining selective b-cell ablation with damage to the exocrine pancreas and find that there is extensive islet cell transdifferentiation in that setting.
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