Pathology and molecular mechanism of embryonic edema in mice carrying endothelial gene mutations

• Project/Area Number: 22590173
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Kobe University
• Principal Investigator: HIRASHIMA Masanori 神戸大学, 大学院・医学研究科, 准教授 (40383757)
• Co-Investigator(Renkei-kenkyūsha): MORIWAKI Kazumasa 神戸大学, 大学院・医学研究科, グローバルCOE 研究員 (00467656) ; DING Guo 神戸大学, 大学院・医学研究科, グローバルCOE 研究員 (00514697)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 発生学 / 形態形成学 / マウス / 遺伝子変異 / 発生 / 胎生期浮腫 / リンパ管 / 血管

Research Abstract

We analyzed vascular permeability and development of the heart, blood vessels, and lymphatic vessels in Aspp1-/- and Flt1+/- mice showing embryonic edema. Lymphatic vascular development is defective in Aspp1-/- embryos, whereas vascular permeability is enhanced in Flt1+/- embryos with enhancement ofFlk1 phosphorylation. Transmission electron microscopic analysis reveals an intricateluminal surface and huge vesicle-like structures in Flt1+/- capillary endothelial cells,suggesting a promoted transcellular transport. Our analysis also shows that defectivelymphatic vessels and enhanced vascular permeability cause embryonic lethality of Aspp1-/-;Flt1+/- mice.

Research Products

• [Journal Article] Flt1 and Flk1 mediate regulation of intraocular pressure and their double heterozygosity causes the buphthalmia in mice (2012)
  • Author(s): Keigo Sano, Osamu Katsuta, Satoshi Shirae, Yoshiaki Kubota, Masatsugu Ema, Toshio Suda, Masatsugu Nakamura and Masanori Hirashima
  • Journal Title: Biochem Biophys Res Commun Volume: 420(2) Issue: 2 Pages: 422-427
  • DOI: 10.1016/j.bbrc.2012.03.011
  • Peer Reviewed
• [Journal Article] Flt1 and Flk1 mediate regulation of intraocular pressure and their double heterozygosity causes the buphthalmia in mice (2012)
  • Author(s): Keigo Sano, Osamu Katsuta, Satoshi Shirae, Yoshiaki Kubota, Masatsugu Ema, Toshio Suda, Masatsugu Nakamura, Masanori Hirashima
  • Journal Title: Biochem Biophys Res Commun Volume: (印刷中)
  • Peer Reviewed
• [Presentation] 血小板はどのようにしてリンパ管網の独自性を守るのか (2012)
  • Author(s): 平島正則
  • Organizer: 第36回日本リンパ学会総会「シンポジウム・リンパ管の形成・機能の発現を左右する重要因子
  • Place of Presentation: 東京女子医科大学(東京都)
  • Year and Date: 2012-06-29
• [Presentation] 血小板はどのようにしてリンパ管網の独自性を守るのか (2012)
  • Author(s): 平島 正則
  • Organizer: 日本リンパ学会
  • Place of Presentation: 東京女子医科大学（東京都）
  • Invited
• [Presentation] Platelets Contribute to the Separation between Blood Vessels and Lymphatic Vessels during Lymphatic Sprouting (2011)
  • Author(s): Guo Ding, Katsue Suzuki Inoue, Osamu Inoue, Masaki Hikida, Tomohiro Kurosaki, Masanori Hirashima
  • Organizer: 第19回日本血管生物医学会学術集会
  • Place of Presentation: 東京ステーションコンファレンス(東京都)
  • Year and Date: 2011-12-09
• [Presentation] Platelets Contribute to the Separation between Blood Vessels and Lymphatic Vessels during Lymphatic Sprouting (2011)
  • Author(s): Guo Ding, Katsue Suzuki Inoue, Osamu Inoue, Masaki Hikida, Tomohiro Kurosaki, Masanori Hirashima
  • Organizer: 日本血管生物医学会
  • Place of Presentation: 東京ステーションコンファレンス(東京都)
  • Year and Date: 2011-12-09
• [Presentation] 体液調節異常と胎生期浮腫をきたす遺伝子変異マウスの解析 (2010)
  • Author(s): 平島正則
  • Organizer: 日本人類遺伝学会第55回大会
  • Place of Presentation: 大宮ソニックシティ(埼玉県)
  • Year and Date: 2010-10-29
• [Presentation] 体液調節異常と胎生期浮腫をきたす遺伝子変異マウスの解析 (2010)
  • Author(s): 平島正則
  • Organizer: 日本人類遺伝学会
  • Place of Presentation: 大宮ソニックシティ(埼玉県)
  • Year and Date: 2010-10-29
• [Presentation] VEGF-A receptors in lymphatic vessel development and fluid homeostasis (2010)
  • Author(s): Masanori Hirashima
  • Organizer: 2010 International Cancer Biology Symposium
  • Place of Presentation: 国立中山大学(台湾)
  • Year and Date: 2010-06-28
• [Presentation] VEGF-A receptors in lymphatic vessel development and fluid homeostasis (2010)
  • Author(s): Masanori Hirashima
  • Organizer: 2010 International Cancer Biology Symposium
  • Place of Presentation: 国立中山大学(台湾)(招待講演)
  • Year and Date: 2010-06-28
• [Presentation] 体液調節異常と胎生期浮腫をきたす遺伝子変異マウスの解析 (2010)
  • Author(s): 平島正則
  • Organizer: 第34回日本リンパ学会総会「シンポジウム・リンパ管新生の最前線」
  • Place of Presentation: 東京大学山上会館(東京都)
  • Year and Date: 2010-06-26
• [Presentation] 体液調節異常と胎生期浮腫をきたす遣伝子変異マウスの解析 (2010)
  • Author(s): 平島正則
  • Organizer: 日本リンパ学会
  • Place of Presentation: 東京大学山上会館(東京都)(招待講演)
  • Year and Date: 2010-06-26
• [Remarks]
  • URL: http://www.med.kobe-u.ac.jp/vascul/index.html