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Application of the gene search system to screen for longevity genes in Drosophila

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Abstract

We have developed a strategy using Drosophila as a model system to identifygenes that are crucial for extension oflongevity. A collection of transgenic lineswith a P-element based gene search (GS)vector containing UAS (Upstream ActivatingSequence) was screened for longevity incombination with an hsp70promoter-driven GAL4 transgene.Misexpression of the vector-flanking sequencewas induced throughout the adult stage to assessits effects on the aging process rather thandevelopment. We showed that the longevity wasgreatly affected by GS inserts, and it waspositively correlated with paraquatresistance. Of 646 GS inserts, we selected 23inserts with relatively longer longevity forfurther molecular analysis. All of themisexpressed sequences matched either knowngenes or ESTs (Expressed Sequence Tags). Among13 genes whose functions are already known orsuggested, six were related to stressresistance or redox balance (DmGST2,hsp26, nla, and Drosophilahomologs of mammalian TRX, GILT and POSH),suggesting the importance of stress resistancefor the extension of longevity. This is thefirst demonstration that a systematicgain-of-function screen could efficientlydetect longevity genes.

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References

  • Adams MD, Celniker SE, Holt RA et al. (2000) The genome sequence of Drosophila melanogaster. Science 287: 2185–2195

    PubMed  Google Scholar 

  • Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W and Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25: 3389–3402

    Article  PubMed  Google Scholar 

  • Andersen SS (2000) Spindle assembly and the art of regulating microtubule dynamics by MAPs and Stathmin/Op18. Trends Cell Biol 10: 261–267

    PubMed  Google Scholar 

  • Arunachalam B, Phan UT, Geuze HJ and Cresswell P (2000) Enzymatic reduction of disulfide bonds in lysosomes: characterization of a gamma-interferon-inducible lysosomal thiol reductase (GILT). Proc Natl Acad Sci USA 97: 745–750

    PubMed  Google Scholar 

  • Asano K, Vornlocher HP, Richter-Cook NJ, Merrick WC, Hinnebusch AG and Hershey JW (1997) Structure of cDNAs encoding human eukaryotic initiation factor 3 subunits. Possible roles in RNA binding and macromolecular assembly. J Biol Chem 272: 27042–27052

    PubMed  Google Scholar 

  • Beall C, Fyrberg C, Song S and Fyrberg E (1992) Isolation of a Drosophila gene encoding glutathione S-transferase. Biochem Genet 30: 515–527

    PubMed  Google Scholar 

  • Butler SJ, Ray S and Hiromi Y (1997) klingon, a novel member of the Drosophila immunoglobulin superfamily, is required for the development of the R7 photoreceptor neuron. Development 124: 781–792

    PubMed  Google Scholar 

  • Crawford DR, Leahy KP, Abramova N, Lan L, Wang Y and Davies KJ (1997) Hamster adapt78 mRNA is a Down syndrome critical region homologue that is inducible by oxidative stress. Arch Biochem Biophys 342: 6–12

    PubMed  Google Scholar 

  • Friedman DB and Johnson TE (1988) A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility. Genetics 118: 75–86

    PubMed  Google Scholar 

  • Fuentes JJ, Pritchard MA, Planas AM, Bosch A, Ferrer I and Estivill X (1995) A new human gene from the Down syndrome critical region encodes a proline-rich protein highly expressed in fetal brain and heart. Hum Mol Genet 4: 1935–1944

    PubMed  Google Scholar 

  • Gil OD, Zanazzi G, Struyk AF and Salzer JL (1998) Neurotrimin mediates bifunctional effects on neurite outgrowth via homophilic and heterophilic interactions. J Neurosci 18: 9312–9325

    PubMed  Google Scholar 

  • Honda Y and Honda S (1999) The daf-2 gene network for longevity regulates oxidative stress resistance and Mnsuperoxide dismutase gene expression in Caenorhabditis elegans. Faseb J 13: 1385–1393

    PubMed  Google Scholar 

  • Kenyon C, Chang J, Gensch E, Rudner A and Tabtiang R (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366: 461–464

    PubMed  Google Scholar 

  • Khare N, Fascetti N, DaRocha S, Chiquet-Ehrismann R and Baumgartner S (2000) Expression patterns of two new members of the Semaphorin family in Drosophila suggest early functions during embryogenesis. Mech Dev 91: 393–397

    PubMed  Google Scholar 

  • Larsen PL (1993) Aging and resistance to oxidative damage in Caenorhabditis elegans. Proc Natl Acad Sci USA 90: 8905–8909

    PubMed  Google Scholar 

  • Lin YJ, Seroude L and Benzer S (1998) Extended life-span and stress resistance in the Drosophila mutant methuselah. Science 282: 943–946

    PubMed  Google Scholar 

  • Marin R, Valet JP and Tanguay RM (1993) hsp23 and hsp26 exhibit distinct spatial and temporal patterns of constitutive expression in Drosophila adults. Dev Genet 14: 69–77

    PubMed  Google Scholar 

  • McGarry TJ and Lindquist S (1986) Inhibition of heat shock protein synthesis by heat-inducible antisense RNA. Proc Natl Acad Sci USA 83: 399–403

    PubMed  Google Scholar 

  • Migliaccio E, Giorgio M, Mele S, Pelicci G, Reboldi P, Pandolfi PP, Lanfrancone L and Pelicci PG (1999) The p66shc adaptor protein controls oxidative stress response and life span in mammals. Nature 402: 309–313

    PubMed  Google Scholar 

  • Morgan NS, Heintzelman MB and Mooseker MS (1995) Characterization of myosin-IA and myosin-IB, two unconventional myosins associated with the Drosophila brush border cytoskeleton. Dev Biol 172: 51–71

    PubMed  Google Scholar 

  • Nicole LM and Tanguay RM (1987) On the specificity of antisense RNA to arrest in vitro translation of mRNA coding for Drosophila hsp 23. Biosci Rep 7: 239–246

    PubMed  Google Scholar 

  • Orr WC and Sohal RS (1994) Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science 263: 1128–1130

    PubMed  Google Scholar 

  • Parkes TL, Elia AJ, Dickinson D, Hilliker AJ, Phillips JP and Boulianne GL (1998) Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons. Nat Genet 19: 171–174

    PubMed  Google Scholar 

  • Spector A, Yan GZ, Huang RR, McDermott MJ, Gascoyne PR and Pigiet V (1988) The effect of H2O2 upon thioredoxin-enriched lens epithelial cells. J Biol Chem 263: 4984–4990

    PubMed  Google Scholar 

  • Sun J and Tower J (1999) FLP recombinase-mediated induction of Cu/Zn-superoxide dismutase transgene expression can extend the life span of adult Drosophila melanogaster flies. Mol Cell Biol 19: 216–228

    PubMed  Google Scholar 

  • Takagi Y, Mitsui A, Nishiyama A, Nozaki K, Sono H, Gon Y, Hashimoto N and Yodoi J (1999) Overexpression of thioredoxin in transgenic mice attenuates focal ischemic brain damage. Proc Natl Acad Sci USA 96: 4131–4136

    PubMed  Google Scholar 

  • Tapon N, Nagata K, Lamarche N and Hall A (1998) A new rac target POSH is an SH3-containing scaffold protein involved in the JNK and NF-kappaB signalling pathways. EMBO J 17: 1395–1404

    PubMed  Google Scholar 

  • Theurkauf WE and Hazelrigg TI (1998) in vivo analyses of cytoplasmic transport and cytoskeletal organization during Drosophila oogenesis: characterization of a multi-step anterior localization pathway. Development 125: 3655–3666

    PubMed  Google Scholar 

  • Toba G, Ohsako T, Miyata N, Ohtsuka T, Seong KH and Aigaki T (1999) The gene search system. A method for efficient detection and rapid molecular identification of genes in Drosophila melanogaster. Genetics 151: 725–737

    PubMed  Google Scholar 

  • Tower J (1996) Aging mechanisms in fruit files. Bioessays 18: 799–807

    PubMed  Google Scholar 

  • Vieira C, Pasyukova EG, Zeng ZB, Hackett JB, Lyman RF and Mackay TF (2000) Genotype-environment interaction for quantitative trait loci affecting life span in Drosophila melanogaster. Genetics 154: 213–227

    PubMed  Google Scholar 

  • Yang Y and Wilson DL (2000) Isolating aging mutants: a novel method yields three strains of the nematode Caenorhabditis elegans with extended life spans. Mech Ageing Dev 113: 101–116

    PubMed  Google Scholar 

  • Yu HH, Araj HH, Ralls SA and Kolodkin AL (1998) The transmembrane Semaphorin Sema I is required in Drosophila for embryonic motor and CNS axon guidance. Neuron 20: 207–220

    PubMed  Google Scholar 

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Seong, KH., Ogashiwa, T., Matsuo, T. et al. Application of the gene search system to screen for longevity genes in Drosophila. Biogerontology 2, 209–217 (2001). https://doi.org/10.1023/A:1011517325711

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