C57BL/6J mice carrying tri-fusion transgene Ins2-luc/EGFP/Tk, commonly called MIP-TF, line 300 express a luciferase/enhanced green fluorescent protein/thymidine kinase fusion protein (luc/EGFP/Tk) under the control of mouse insulin promoter (Ins2) and are viable, fertile and exhibit no gross physical or behavioral abnormalities. Transgene expression, determined by luciferase enzymatic activity and green fluorescence is exclusive to the pancreas, specifically the insulin producing cells.  Transgene expression appears to have no effect on weight, islet morphology, fasting blood glucose, or response to glucose challenge when compared to wild-type controls.  This trifusion reporter model should enable longitudinal noninvasive imaging of beta cells in the same animal by cooled charge coupled device (CCD) and micro positron emission tomography (microPET), and identification of beta cells at the cellular level by fluorescent microscopy.  There is a correlation between CCD and microPET signals from the pancreas region of the individual transgenic mice.  After low dose streptozotocin treatment to induce type 1 diabetes, there is a reduction in the bioluminescence signals from the pancreas prior to the appearance of hyperglycemia.  Conversely, pancreatic bioluminescence signals from the pancreas progressively increase (3.6 fold higher compared to control mice) in mice fed a high fat diet to model early type 2 diabetes.  This transgenic model provides a new tool for monitoring beta cells from the single cell level to non-invasive longitudinal assessments of beta cells in animal models of type 1 diabetes and type 2 diabetes.

B6.MIP-TF mice harbor the tri-fusion transgene of three imaging reporters, luciferase/EGFP/thymidine kinase, under the control of mouse insulin promoter. Longitudinal noninvasive imaging of beta cells in the same transgenic animal by CCD and microPET, and the identification of beta cells at the cellular level by fluorescent microscopy is possible. This transgenic model provides a new tool for monitoring beta cells from the single cell level to non-invasive longitudinal assessments of beta cells in animal models of type 1 diabetes and type 2 diabetes. 

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