title: A gain-of-function screen to identify genes that reduce lifespan in the adult of Drosophila melanogaster.
abstract: BACKGROUND
  Several lines of evidence associate misregulated genetic expression with risk factors for diabetes, Alzheimer's, and other diseases that sporadically develop in healthy adults with no background of hereditary disorders. Thus, we are interested in genes that may be expressed normally through parts of an individual's life, but can cause physiological defects and disease when misexpressed in adulthood.
  
  
  RESULTS
  We attempted to identify these genes in a model organism by arbitrarily misexpressing specific genes in adult Drosophila melanogaster, using 14,133 Gene Search lines. We identified 39 "reduced-lifespan genes" that, when misexpressed in adulthood, shortened the flies' lifespan to less than 30% of that of control flies. About half of these genes have human orthologs that are known to be involved in human diseases. For about one-fourth of the reduced-lifespan genes, suppressing apoptosis restored the lifespan shortened by their misexpression. We determined the organs responsible for reduced lifespan when these genes were misexpressed specifically in adulthood, and found that while some genes induced reduced lifespan only when misexpressed in specific adult organs, others could induce reduced lifespan when misexpressed in various organs. This finding suggests that tissue-specific dysfunction may be involved in reduced lifespan related to gene misexpression. Gene ontology analysis showed that reduced-lifespan genes are biased toward genes related to development.
  
  
  CONCLUSIONS
  We identified 39 genes that, when misexpressed in adulthood, shortened the lifespan of adult flies. Suppressing apoptosis rescued this shortened lifespan for only a subset of the reduced-lifespan genes. The adult tissues in which gene misexpression caused early death differed among the reduced-lifespan genes. These results suggest that the cause of reduced lifespan upon misexpression differed among the genes.
authors.forename: Minoru
authors.initials: M
authors.lastname: Nakayama
authors.forename: Tomoki
authors.initials: T
authors.lastname: Ishibashi
authors.forename: Hiroyuki O
authors.initials: HO
authors.lastname: Ishikawa
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Sato
authors.forename: Takao
authors.initials: T
authors.lastname: Usui
authors.forename: Takayuki
authors.initials: T
authors.lastname: Okuda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yashiro
authors.forename: Hironori
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Taikou
authors.forename: Asako
authors.initials: A
authors.lastname: Minami
authors.forename: Kengo
authors.initials: K
authors.lastname: Kato
authors.forename: Masataka
authors.initials: M
authors.lastname: Taki
authors.forename: Toshiro
authors.initials: T
authors.lastname: Aigaki
authors.forename: Wataru
authors.initials: W
authors.lastname: Gunji
authors.forename: Masaya
authors.initials: M
authors.lastname: Ohtsu
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Murakami
authors.forename: Sei-Ichi
authors.initials: S
authors.lastname: Tanuma
authors.forename: Alice
authors.initials: A
authors.lastname: Tsuboi
authors.forename: Mai
authors.initials: M
authors.lastname: Adachi
authors.forename: Junpei
authors.initials: J
authors.lastname: Kuroda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sasamura
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamakawa
authors.affiliation: Department of Biological Sciences, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan. kmatsuno@bio.sci.osaka-u.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsuno
mesh_terms: D000818:Animals; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development*; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D005804:Genes, Lethal; D008136:Longevity / Q000235:genetics*; D008297:Male
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