We generated a transgenic mouse expressing the luciferase optical reporter under control of the mouse insulin I promoter (MIP-Luc-VU) and characterized this model in mice with increased or decreased β cell mass and after islet transplantation.  MIP-Luc-VU mice emitted strong and consistent bioluminescence emanating exclusively from β cells of the pancreatic islet.  MIP-Luc-VU islets had normal islet architecture and secreted insulin normally in vivo and in vitro. By tracking changes in β cell mass using bioluminescence imaging (BLI) and post-mortem metrics, streptozotocin-induced, diabetic MIP-Luc-VU mice had a progressive decline in bioluminescence that correlated with a decrease in pancreatic insulin content and β cell mass.  MIP-Luc-VU animals fed a high fat diet displayed a progressive increase in bioluminescence that reflected an immunohistochemically verified increase in β cell mass.  MIP-Luc-VU islets transplanted beneath the renal capsule or into the liver emitted bioluminescence proportional to the number of islets transplanted and graft insulin content and could be imaged for more than a year.  Since bioluminescence in the MIP-Luc-VU mouse model is proportional to β cell mass in the setting of increased and decreased β cell mass and after transplantation, this approach should be useful for non-invasively assessing β cell mass in pre-clinical mouse models of glucose homeostasis, β cell growth and regeneration, and diabetes.

A vector with the 9.2 kb mouse insulin I promoter (MIP was used (MIP promoter from Mark Magnuson - see Am J Physiol Endocrinol Metab 284: E177-183, 2003). The luciferase cDNA was released from the blue script vector (Stratagene, La Jolla, CA) by digestion with Kpm I and Not I, purified by agarose gel electrophoresis, and subcloned into a vector containing the MIP fragment and beta globin fragment.

The purified DNA was injected by the Vanderbilt University Transgenic / ES core into Friend leukemia Virus B strain (FVB/NJ, Jackson Labs, Bar Harbor, ME) mouse embryos.