Identifying candidate genes for a mutation that suppresses neurodegeneration in the Drosophila model of Leigh syndrome
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Mitochondrial dysfunction is involved in many neurodegenerative diseases in humans. The levy 1 mutation is the first case ever reported of a mutation that occurs in the nuclear encoded structural subunit of COX, leading to encephalomyopathic effects rather than lethality in Drosophila . Recently, a suppressor mutation [ Su(levy) ] has been identified that partially rescues the detrimental effects of the levy 1 mutation. However, the identity of the Su(levy) mutation and its location is still currently unknown. Here, we report the region where the Su(levy) mutation is believed to be located and propose candidate genes for the Su(levy) mutation. The data from recombination mapping and deficiency mapping studies indicate that the Su(levy) mutation exists within the interval region 43F1-43F4. Furthermore, there are 8 genes within this region: lin19, Or43b, Kdm4A, CG8791, CG30381, rnh1, drosha, and CG8728 . This finding has been confirmed using S 1 Df(2R)BSC265 levy 1 Pin Yt / + + levy 1 + mutant flies, which were subjected to behavioral tests (temperature-induced-paralysis test and life expectancy test). The identification of the Su(levy) mutation is of significance because this modifier mutation can provide further leads into the pathway(s) disrupted by levy . Since the Su(levy) mutation partially rescues Drosophila from neurodegeneration and other phenotypical characteristics known to be associated with levy such as paralysis time and lifespan, it is most likely to be involved in the pathway of levy . In addition, identifying the Su(levy) gene will allow researchers to explore potential therapeutic treatments for mitochondrial encephalomyopathies caused by COX deficiency. Further, an understanding of how the Su(levy) mutation ameliorates neurodegeneration may help reveal steps in the pathway(s) leading to mitochondrial encephalomyopathy seen in levy 1 mutants.