Functional Analysis of large MAF Transcription Factors in Endocrine Pancreas

• Project/Area Number: 26460356
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Nagoya City University (2016); University of Tsukuba (2014-2015)
• Principal Investigator: OISHI Hisashi 名古屋市立大学, 大学院医学研究科, 教授 (30375513)
• Co-Investigator(Kenkyū-buntansha): 高橋 智 筑波大学, 医学医療系, 教授 (50271896)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: インスリン / 大Maf転写因子 / 膵内分泌細胞 / 糖尿病 / 大Maf群転写因子

Outline of Final Research Achievements

In this study, the functional similarity and difference of large Maf transcription factors has been elucidated in endocrine pancreas. The phenotypic comparison among MafA(-/-), β-cell specific MafB(-/-), and MafA(-/-);MafB(+/-) mice revealed that: (1) MafA gene was important for the maturation of β-cell function but not for β-cell development, (2)conversely, MafB gene was important for the normal β-cell development, and β-cell specific MafB(-/-) mice in adult showed no obvious abnormality including fasting blood glucose levels and glucose stimulated insulin secretion.
In addition, in order to apply diabetic treatment of large Maf genes, MafA or MafB gene together with other β-cell related genes were transferred in to mouse liver. The result demonstrated MafA is capable to induce more effective β-like cell induction than MafB.

Research Products

• [Int'l Joint Research] National Taiwan University(Taiwan)
• [Int'l Joint Research] Cairo University(Egypt)
• [Int'l Joint Research] mansoura university(Egypt)
• [Journal Article] Generation of CRISPR/Cas9-mediated bicistronic knock-in <i>ins1-cre</i> driver mice (2016)
  • Author(s): Yoshikazu Hasegawa, Yoshikazu Hoshino, Abdelaziz E. Ibrahim, Kanako Kato, Yoko Daitoku1, Yoko Tanimoto, Yoshihisa Ikeda, Hisashi Oishi, Satoru Takahashi, Atsushi Yoshiki, Ken-ichi Yagami, Hiroyoshi Iseki, Seiya Mizuno, Fumihiro Sugiyama
  • Journal Title: Experimental Animals Volume: 65 Issue: 3 Pages: 319-327
  • DOI: 10.1538/expanim.16-0016
  • NAID: 130006882371
  • ISSN: 0007-5124, 1341-1357, 1881-7122
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] β-Cell-Specific Mafk Overexpression Impairs Pancreatic Endocrine Cell Development. (2016)
  • Author(s): Ahmed M. Abdellatif, Hisashi Oishi , Takahiro Itagaki, Yunshin Jung, Hossam H. Shawki, Yukari Okita, Yoshikazu Hasegawa, Hiroyuki Suzuki, Salah E. El-Morsy, Mesbah A. El-Sayed, Mahmoud B. Shoaib, Fumihiro Sugiyama, Satoru Takahashi
  • Journal Title: PLoS One. Volume: 11 Issue: 2 Pages: e0150010-e0150010
  • DOI: 10.1371/journal.pone.0150010
  • NAID: 120007129599
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of large MAF transcription factors in the mouse endocrine pancreas (2015)
  • Author(s): Abdellatif AM, Ogata K, Kudo T, Xiafukaiti G, Chang YH, Katoh MC, El-Morsy SE, Oishi H, Takahashi S.
  • Journal Title: Experimental Animals Volume: 64 Issue: 3 Pages: 305-312
  • DOI: 10.1538/expanim.15-0001
  • NAID: 130005091028
  • ISSN: 0007-5124, 1341-1357, 1881-7122
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] MafB antagonizes phenotypic alteration induced by GM-CSF in microglia. (2015)
  • Author(s): Koshida R, Oishi H, Hamada M, Takahashi S.
  • Journal Title: Biochem Biophys Res Commun. Volume: 463 Issue: 1-2 Pages: 109-115
  • DOI: 10.1016/j.bbrc.2015.05.036
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] β-Cell-Specific Mafk Overexpression Impairs Pancreatic Endocrine Cell Development. (2015)
  • Author(s): Abdellatif AM, Oishi H, Itagaki T, Jung Y, Shawki HH, Okita Y, Hasegawa Y, Suzuki H, El-Morsy SE, El-Sayed MA, Shoaib MB, Sugiyama F, Takahashi S.
  • Journal Title: PLoS One Volume: 11
  • NAID: 120007129599
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Generation and characterization of MafA-Kusabira Orange mice (2015)
  • Author(s): Nishimura W, Oishi H, Funahashi N, Fujiwara T, Takahashi S, Yasuda K.
  • Journal Title: Endocrine Journal Volume: 62 Issue: 1 Pages: 37-51
  • DOI: 10.1507/endocrj.EJ14-0296
  • NAID: 130004694063
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed
• [Journal Article] Generation of insulin-producing cells from the mouse liver using β cell-related gene transfer including Mafa and Mafb. (2014)
  • Author(s): Nagasaki H, Katsumata T, Oishi H, Tai PH, Sekiguchi Y, Koshida R, Jung Y, Kudo T, Takahashi S.
  • Journal Title: PLoS One Volume: 9 Issue: 11 Pages: e113022-e113022
  • DOI: 10.1371/journal.pone.0113022
  • Peer Reviewed / Open Access
• [Journal Article] MafA is required for postnatal proliferation of pancreatic β-cells. (2014)
  • Author(s): Eto K, Nishimura W, Oishi H, Udagawa H, Kawaguchi M, Hiramoto M, Fujiwara T, Takahashi S, Yasuda K.
  • Journal Title: PLoS One. Volume: 15 Issue: 8 Pages: e104184-e104184
  • DOI: 10.1371/journal.pone.0104184
  • Peer Reviewed / Open Access
• [Presentation] In vivo イメージングによる膵β細胞の可視化 (2016)
  • Author(s): 大石 久史, 逆井 智貴、Jung Yunshin、周 如意 三輪 佳宏、高橋 智
  • Organizer: 第121回 日本解剖学会総会
  • Place of Presentation: 福島県郡山市ビッグパレット福島
  • Year and Date: 2016-03-28
  • Invited
• [Presentation] Large Maf transcripon factors in endocrine pancreas and their role in diabetes (2015)
  • Author(s): Hisashi Oishi
  • Organizer: ISCA-Japan meeting
  • Place of Presentation: Dublin, Irland
  • Year and Date: 2015-09-08
  • Int'l Joint Research / Invited
• [Remarks] 名古屋市立大学大学院医学研究科病態モデル医学分野
  • URL: http://www.med.nagoya-cu.ac.jp/w3med/labo/byotai.dir/index.html