Homeostasis of retinal pigment epithelium essential for survival of photorecptor cells

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659123
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: Tohoku University
• Principal Investigator: SHIBAHARA Shigeki 東北大学, 医学(系)研究科(研究院), 教授 (00154253)
• Co-Investigator(Kenkyū-buntansha): TAKEDA Kazuhisa 東北大学, 大学院医学系研究科, 准教授 (30311559) ; FURUYAMA Kazumichi 岩手医科大学, 医学部, 教授 (80280874)
• Co-Investigator(Renkei-kenkyūsha): YOSHIZAWA Miki 東北大学, 大学院医学系研究科, 技術専門職員 (50221669)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 網膜色素上皮 / 転写因子 / メラニン / L1エレメント / MITF / 生体防御 / ストレス応答

Research Abstract

Microphthalmia-associated transcription factor (Mitf) is required for differentiation of retinal pigment epithelium. The mouse homozygous for the black-eyed white (Mitf-bw) allele is characterized by white-coat color and deafness with black eye, due to the loss of melanoblasts. The Mitf-bw allele carries an insertion of L1 element in the Mitf gene, causing the deficiency of the melanocyte-specific Mitf-M. Moreover, alternatively spliced Mitf-M mRNA species are expressed in developing melanoblasts: Mitf-M mRNA lacking exon 3, exon 4, or both exons 3 and 4. These aberrant mRNAs are also expressed in the bw mouse brain. Importantly, Mitf-M mRNA is expressed in the mouse and human brain. Moreover, the bw mice show the altered volitional motor activity under a stressful environment.
We identified the MITF isoform expressed in the human retinal pigment epithelium. Moreover, the beta-catenin is responsible for maintaining the expression of MITF in the retinal pigment epithelium.

Research Products

• [Journal Article] Insertion of long interspersed element-1 in the Mitf gene is associated with altered neurobehavior of the black-eyed white Mitf^<mi-bw>mouse (2014)
  • Author(s): Takeda K, Hozumi H, Nakai K, Yoshizawa M, Satoh H, Yamamoto H, Shibahara S
  • Journal Title: Genes Cells Volume: 19 Pages: 126-140
  • DOI: 10.1111/gtc.12117
  • Peer Reviewed
• [Journal Article] Otx2 is involved in the regional specification of the developing retinal pigment epithelium by preventing the expression of Sox2 and Fgf8, factors that induce neural retina differentiation (2012)
  • Author(s): Nishihara D, Yajima I, Tabata H, Nakai M, Tsukiji N, Katahira T, Takeda K, Shibahara S, Nakamura H, Yamamoto H
  • Journal Title: PLoS One Volume: 7(11) Pages: e48879
  • DOI: 10.1371/journal.pone.0048879
  • Peer Reviewed
• [Presentation] black-eyed white Mitf^<mi-bw>mouseにおけるMitf-M mRNAのスプライシング異常と行動異常 (2013)
  • Author(s): 武田和久、穂積大貴、仲井邦彦、吉澤美季、山本博章、柴原茂樹
  • Organizer: 第25回日本色素細胞学会年次学術大会
  • Place of Presentation: 大阪大学
  • Year and Date: 20131116-17
• [Presentation] An insertion of long interspersed element-1 in the Mitf gene is associated with altered volitional motor activity of the black-eyed white Mitf^<mi-bw>mouse (2013)
  • Author(s): Kazuhisa Takeda, Hiroki Hozumi, Kunihiko Nakai, Miki Yoshizawa, Hiroshi Satoh, Hiroaki Yamamoto, Shigeki Shibahara
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜パシフィコ
  • Year and Date: 20130911-13
• [Presentation] 聴覚•色素異常を呈するblack-eyed white Mitf^<mi-bw>mouseのメラノブラスト分化異常 (2012)
  • Author(s): 穂積大貴、武田和久、天野恭子、東谷篤志、山本博章、柴原茂樹
  • Organizer: 第35回日本分子生物学会年次学術大会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 20121211-14
• [Presentation] Melanocyte-specific Mitf-M is a key regulator for development of melanoblasts : Lessons from the black-eyed white Mitf^<mi-bw>mouse (2012)
  • Author(s): Kazuhisa Takeda, Hiroki Hozumi, Yasuko Yoshida-Amano, Atushi Higashitani, Hiroaki Yamamoto, Shigeki Shibahara
  • Organizer: 第24回日本色素細胞学会年次学術大会
  • Place of Presentation: 長浜バイオ大学
  • Year and Date: 20121124-25
• [Remarks]
  • URL: http://www.mbap.med.tohoku.ac.jp/