Establishment of induction method for Insulin producing cells by overexpression of large Maf transcription factors

2011 Fiscal Year Final Research Report

• Project/Area Number: 22650090
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Laboratory animal science
• Research Institution: University of Tsukuba
• Principal Investigator: TAKAHASHI Satoru 筑波大学, 医学医療系, 教授 (50271896)
• Project Period (FY): 2010 – 2011
• Keywords: 実験動物学

Research Abstract

We examined whether in vivo bioluminescence imaging (BLI) could monitor the dynamics of insulin promoter activity in extrapancreatic tissues, especially in the liver. To do this, hepatocytes of MIP-Luc mice, in which luciferase reporter gene expresses under the control of mouse insulin gene promoter, were transduced in vivo with recombinant adenovirus expressing defined transcription factors related to insulin transcription, Pdx1, NeuroD, and MafA or MafB. The bioluminescent signal from the liver was detected in mice infected with all of three genes until about a week after the infection. Immunohistochemical analysis of the liver infected with combination of Pdx1, NeuroD, and MafA recombinant adenoviruses revealed the presence of some insulin positive cells consistent with the enhanced BLI signal intensity. These results suggest that the BLI signal emitted from the liver region of the MIP-Luc mice is useful for the monitoring the insulin promoter activity and Pdx1, NeuroD, and MafA have activity to induce insulin transcription.

Research Products

• [Journal Article] Non-invasive monitoring of υ-cell mass and fetal υ-cellgenesis in mouse using bioluminescence imaging (2012)
  • Author(s): Sekiguchi Y, Owada J, Oishi H, Katsumata T, Ikeda R, Kudo T, Takahashi S
  • Journal Title: Exp Animal Volume: in press
• [Journal Article] A novel diabetes mellitus mouse model, MafA-deficient and beta cell-specific MafK-overexpressing hybrid transgenic mice, developed severe diabetic nephropathy and improved with TCV-116 (candesartan cilexetil) treatment (2012)
  • Author(s): Fujita A, Yoh K, Shimohata H, Morito N, Ojima M, Okamura M, Takahashi S, Yamagata K
  • Journal Title: Exp Animal Volume: 61 Pages: 49-57
• [Journal Article] MafB interacts with Gcm2 and regulates parathyroid hormone expression and parathyroid development (2011)
  • Author(s): Kamitani-Kawamoto A, Hamada M, Moriguchi T, Miyai M, Hitoshi S, Ikenaka K, Hosoya T, Hotta Y, Takahashi S, Kataoka K
  • Journal Title: J Bone MineralRes Volume: 26 Pages: 2463-2472
• [Journal Article] c-Maf is indispensable for the microenvironment of definitive erythropoiesis as it forms erythroblastic islands in fetal liver (2011)
  • Author(s): Kusakabe M, Hasegawa K, Hamada M, Nakamura M, Ohsumi T, Suzuki H, Kudo T, Uchida K, Ninomiya H, Chiba S, Takahashi S
  • Journal Title: Blood Volume: 118 Pages: 1374-1385
• [Journal Article] A novel transgenic mouse model of the human multiple myeloma chromosomal translocationt (2011)
  • Author(s): Morito N, Yoh K, Maeda A, Nakano T, FujitaA, Kusakabe M, Hamada M, Kudo T, Yamagata K, Takahashi S
  • Journal Title: Cancer Res Volume: 71 Pages: 339-348
• [Journal Article] Maf mediates the age-related switch in mesenchymal cell differentiation (2010)
  • Author(s): Nishikawa K, Nakashima T, Takeda S, Isogai M, Hamada M, Kimura A, Kodama T, Yamaguchi A, Owen MJ, Takahashi S, Takayanagi H
  • Journal Title: JClin Invest Volume: 120 Pages: 3455-3465
• [Journal Article] Insulin transactivator MafA regulates intra-thymic expression of insulin and affects susceptibility to type 1 diabetes (2010)
  • Author(s): Noso S, Kataoka K, Kawabata Y, Babaya N, Hiromine Y, Yamaji K, Fujisawa T, Aramata S, Kudo T, Takahashi S, Ikegami H
  • Journal Title: Diabetes Volume: 59 Pages: 2579-2587
• [Presentation] In vivo monitoring of intra-hepatic insulin gene activity bybioluminescence imaging (2012)
  • Author(s): Sekiguchi Y, Oishi H, Katsumata T, NagasakiH, Kudo T, Takahashi S
  • Organizer: 分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 20121213-16
• [Presentation] Bioluminescence imaging of novel BAC transgenic mice expressing luciferase reporter gene under the control of the insulin locus (2012)
  • Author(s): Katsumata T, Oishi H, Sekiguchi Y, NagasakiH, Ema M, Kudo T, Takahashi S
  • Organizer: 分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 20121213-16
• [Remarks]
  • URL: http://www.md.tsukuba.ac.jp/basic-med/anatomy/embryology/index.html