Noninvasive monitoring of ß-cell mass and fetal ß-cell genesis in mice using bioluminescence imaging.

ABSTRACT

Bioluminescence imaging (BLI) has been applied in gene therapy and research to screen for transgene expression, progression of infection, tumor growth and metastasis, and transplantation. It enables real-time and relatively noninvasive localization and serial quantification of biological processes in experimental animals. In diabetes research, BLI has been employed for the quantification of ß-cell mass, monitoring of islet graft survival after transplantation, and detection of reporter gene expression. Here, we explore the use of BLI in a transgenic mouse expressing luciferase under the control of the mouse insulin 1 promoter (MIP-Luc-VU). A previous report on MIP-Luc-VU mice showed luminescence intensities emitted from the islets correlated well with the number of islets in vitro and in vivo. In this study, we showed MIP-Luc-VU mice fed a high fat diet for 8 weeks gave rise to a greater bioluminescent signal than mice fed a regular diet for the same period of time. Conversely, there was a strong reduction in the signal observed in diabetic Mafa-deficient/Mafk-transgenic mutant mice and streptozotocin-treated mice, reflecting the loss of ß-cells. Furthermore, we were able to monitor fetal ß-cell genesis in MIP-Luc-VU mice during the late gestational stage in a noninvasive and repetitive manner. In summary, we show that bioluminescence imaging of mice expressing a ß-cell specific reporter allows detection of changes in ß-cell mass and visualization of fetal ß-cell neogenesis in uteri.