title: Noninvasive monitoring of β-cell mass and fetal β-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 β-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 β-cells. Furthermore, we were able to monitor fetal β-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 β-cell specific reporter allows detection of changes in β-cell mass and visualization of fetal β-cell neogenesis in uteri.
authors: Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, 1–1–1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors: Yukari
authors: Y
authors: Sekiguchi
authors: Junya
authors: J
authors: Owada
authors: Hisashi
authors: H
authors: Oishi
authors: Tokio
authors: T
authors: Katsumata
authors: Kaori
authors: K
authors: Ikeda
authors: Takashi
authors: T
authors: Kudo
authors: Satoru
authors: S
authors: Takahashi
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D005260:Female; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000473:pathology*; D008156:Luciferases / Q000378:metabolism; D008163:Luminescent Measurements / Q000379:methods*; D051473:Maf Transcription Factors, Large / Q000378:metabolism; D050985:MafK Transcription Factor / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D057054:Molecular Imaging / Q000379:methods*; D011247:Pregnancy; D013047:Specific Pathogen-Free Organisms; D013311:Streptozocin / Q000008:administration & dosage; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D018398:Homeodomain Proteins; D051473:Maf Transcription Factors, Large; D050985:MafK Transcription Factor; C485160:Mafa protein, mouse; C494696:Mafk protein, mouse; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D013311:Streptozocin; D008156:Luciferases