Understanding the pathology of peroxisomal diseases

• Project/Area Number: 25860855
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Gifu University
• Principal Investigator: Takashima Shigeo 岐阜大学, 生命科学総合研究支援センター, 助教 (50537610)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ペルオキシソーム形成異常症 / 疾患モデル動物 / PEX遺伝子 / 先天性代謝異常症 / 極長鎖脂肪酸 / ゼブラフィッシュ / ペルオキシソーム / フィタン酸 / プラズマローゲン

Outline of Final Research Achievements

Peroxisomal biogenesis disorder (PBD) is a congenital metabolic disease mainly appear in newborns and infants. A fish disease model was established using the zebrafish and analyzed in this work. Disease-related PEX2 gene was mutated in zebrafish using a genome editing technique and two disease model fish lines were recovered, each of them possesses a strong mutation or a weak mutation of PEX2 gene. The fish with the strong mutation died in 1-2 months after birth while with the weak mutation survived around 8 months old and then died, recapitulating human patients who have a strong or a weak mutation. A deformation of the liver was found in the disease-model fish and a swimming defect was also manifested. Metabolic abnormality was also found such as an abnormally higher amount of tissue very-long chain fatty acids that is also remarkable in the human patients of this disease. With this model fish, a further analysis will be performed for understanding the detailed pathology of PBD.

Research Products

• [Presentation] ペルオキシソーム形成異常症モデルゼブラフィッシュの表現型解析 (2015)
  • Author(s): 高島茂雄, 豊吉佳代子, 本田綾子, 大場亜希子, 下澤伸行
  • Organizer: 第57回日本先天代謝異常学会総会・第13回アジア先天代謝異常症シンポジウム
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2015-11-12
• [Presentation] LC／MSを用いたペルオキシソーム病関連因子の解析 (2015)
  • Author(s): 高島茂雄, 伊藤貴洋, 吉田敏, 下澤伸行
  • Organizer: 第57回日本先天代謝異常学会総会・第13回アジア先天代謝異常症シンポジウム
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2015-11-12
• [Presentation] Analysis of phathology of peroxisomal biogenesis disorder (2014)
  • Author(s): Shigeo Takashima, Kayoko Toyoshi, Takahiro Ito, Naomi Kajiwara, Akiko Ohba, Ayako Honda, Satoshi Yoshida, Nobuyuki Shimozawa
  • Organizer: 第56回 日本先天代謝異常学会, The 12th Annual Symposium of the Asian Society for Inherited Metabolic Diseases
  • Place of Presentation: Koyo Grand Hotel, Sendai, Japan
  • Year and Date: 2014-11-13 – 2014-11-15
• [Presentation] Zebrafish as a model system to understand the pathology of peroxisomal diseases (2013)
  • Author(s): Shigeo Takashima, Kayoko Toyoshi, Nobuyuki Shimozawa
  • Organizer: The 3rd Asian Congress for Inherited Metabolic Diseases (ACIMD)/The 55th Annual Meeting of The Japanese Society for Inherited Metabolic Diseases (JSIMD)
  • Place of Presentation: Tokyo Bay Maihama Hotel Club Resort, Chiba, Japan
• [Remarks] 高島グループ
  • URL: http://stakashimaj.blogspot.jp/