Figure 1. Generation of INS^CremTmG mice for detection of β cell neogenesis.

(A) Schematic of the INS^CremTmG model. In these mice, all cells are mT⁺ except for the INS⁺ cells that are mG⁺. When non-β mT⁺ cells (β cell progenitors) first start to express the insulin promoter, there is a period during which the cells are still mT⁺, but now express mG, and hence appear yellow (mT⁺mG⁺). This model should allow for the detection of any neogenesis scenario in which β cells were recently generated from non-β cells. Simple replication of preexisting INS⁺ cells does not involve a yellow cell stage, as they are already green prior to replication, and over time express the red fluorescent protein. (B) Representative images under a dissecting fluorescence microscope of E15.5, P5 and the ligated tail pancreas 1 week after PDL. Green mG⁺ cells can be visualized among the red mT⁺ cells in these conditions. Scale bar: 200 μm.