The Drosophila model of Maple Syrup Urine Disease

• Main Authors: Yu-Min Chen, 陳育岷
• Other Authors: Chun-Hong Chen
• Format: Others
• Language: en_US
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/kuzud5

碩士 === 國立臺灣大學 === 分子與細胞生物學研究所 === 105 === The congenital metabolic disorder disease is a very common disease in Taiwan infant. This disease group includes the alteration of carbohydrates and amino acid metabolisms, such as galactosemia, glycogen storage disease, phenylketonuria, diabetes mellitus and maple syrup urine disease. Because the pathogenesis is not clear, diet control is the most common therapy strategy for patients. Patients control their food intakes to prevent these disease outbreak. In this research, Drosophila was used as animal models to mimic the symptoms of branched-chain α-keto acid dehydrogenase complex (BCKAD complex) dysfunction which correlates with the maple syrup urine disease (MSUD) to find the cure strategy. In Drosophila, three Branch-Chain amino acid (BCAA) catabolic enzymes called CG1673, CG5599, and CG8199. These three enzymes are homologs with branch chain aminotransferase, dihydro lipoyl transacylase (E2) and branched-chain alpha-keto acid decarboxylase (E1) in human were selected. Using CRISPR/Cas9 technology, three kinds of gene mutation flies were established. The results showed that the branched chain amino acids in hemolymph in mutant flies were higher than wild type. And their brain damage and climbing ability defect were more serious than wild type. In the experiment, fat storage problem was observed in these flies which had never been reported yet. At the same time, feeding rapamycin could rescue their lifespan and climbing abilities defect in mutant flies. Finally, the microRNA-277 which was one of the upstream controllers of BCAA catabolism pathway also be found in this research. Because of these reasons, these Drosophila models help us to know more about MSUD mechanisms, complications, the upstream and downstream of BCAA catabolic and even drug test more quickly.