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[摘要]：Mitochondrial trifunctional protein (MTP), which consists of the MTP alpha and MTP beta subunits, catalyzes long-chain fatty acid beta-oxidation. MTP deficiency in humans results in Reye-like syndrome. Here, we generated Drosophila models of MTP deficiency by targeting two genes encoding Drosophila homologs of human MTP alpha and MTP beta, respectively. Both Mtp alpha(KO) and Mtp beta(KO) flies were viable, but demonstrated reduced lifespan, defective locomotor activity, and reduced fecundity represented by the number of eggs laid by the females. The phenotypes of Mtp alpha(KO) flies were generally more striking than those of Mtp beta(KO) flies. Mtp alpha(KO) flies were hypersensitive to fasting, and retained lipid droplets in their fat body cells as in non-fasting conditions. The amount of triglyceride was also unchanged upon fasting in Mtp alpha(KO) flies, suggesting that lipid mobilization was disrupted. Finally, we showed that both Mtp alpha(KO) and Mtp beta(KO) flies accumulated acylcarnitine and hydroxyacylcarnitine, diagnostic markers of MTP deficiencies in humans. Our results indicated that both Mtp alpha(KO) and Mtp beta(KO) flies were impaired in long-chain fatty acid beta-oxidation. These flies should be useful as a model system to investigate the molecular pathogenesis of MTP deficiency. (C) 2012 Elsevier Inc. All rights reserved. |
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