Understanding the pathology of peroxisomal diseases

2015 Fiscal Year Final Research Report

• 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
• 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

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.

Free Research Field

発生遺伝学