探討長壽果蠅EP1130的標的基因及其調控機轉

The investigation of the target gene and the possible regulatory mechanisms in Drosophila longevity EP1130

劉雅玲(Ya-Ling Liu)

指導教授 ： 汪宏達

國立清華大學/生命科學院/生物科技研究所/碩士(2007年)

https://doi.org/10.6843/NTHU.2007.00418

摘要

EP1130 為一株經過多重壓力測試所篩選出來具有抗壓性且為長壽的突變株果蠅。而其P-element的插入造成了CG32684( alpha-mannosidase-I ) 表現量降低。其他突變株果蠅: EP1628 和EP982,他們的P-element也是插在CG32684，同樣地，也使得此基因表現量降低且同時他們有長壽的特性及對壓力有抗性。另外一株從多重壓力測試篩選出具有抗壓性的突變株果蠅EP1588其P-element的插入造成CG32684 paralogue基因CG3810表現量減少且也是長壽果蠅。而且我們發現，這些突變株果蠅當為heterozygous基因型態時就足以使得壽命延長。然而，當EP1130，1628 和982在transheterozygous基因型態時並不能使得已延長的壽命再增加。處理alpha-mannosidase-I 活性抑制劑1-deoxymannojirimycin或kifunensine 發現也對果蠅的壽命有正面的效果。藉由分子生物技術及遺傳方法研究探討可能相關的訊息路徑及機制，例如：insulin/IGF-1, JNK pathway, ER stress，然而，目前發現在利用遺傳方法的結果指出EP1130 的長壽可能和ecdysone 路徑有關。總之，我們的研究證實alpha-mannosidase-I的確參與調節果蠅的壽命。

關鍵字

longevity ； aging ； alpha-mannosidase-I ； lifespan ； stress resistance ； fly

並列摘要

The long-lived mutant strain EP1130 was screened from a multiple-stresses test. The P-element inserted in EP1130 down-regulating the expression of alpha-mannosidase-I (CG32684). Independent EP insertion alleles in the CG32684, EP1628 and 982 with reduced expression of alpha-mannosidase-I also showed increase of lifespan and stress resistances. EP1588 is another EP line screened from the multiple-stresses test associated with CG3810, which is a CG32684 paralogue, showed decreased expression and also displayed extended lifespan. We also found heterozygous mutants in these four mutant lines were sufficient for long-lived phenotype. Transheterozygotes among EP1130, 1628, and 982 do not show further enhancement of lifespan compared to homozygous strains. The treatments of alpha-mannosidase-I inhibitors, 1-deoxynojirimycin or kifunensine also showed beneficial effects on lifespan elongation in Drosophila melanogaster. Using molecular and genetic approaches, we found that longevity in EP1130 was independent from insulin/IGF-1, JNK pathway and ER stress. However, the genetics data suggested that it might be involved with ecdysone pathway. In conclusion, this study demonstrated that alpha-mannosidase-I plays a role in regulating lifespan in Drosophila melanogaster.

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