Drosophila, a golden bug, for the dissection of the genetic basis of tolerance and susceptibility to hypoxia.
We have previously discovered that the adult Drosophila melanogaster is tolerant to a low O2 environment, withstanding hours of total O2 deprivation without showing any evidence of cell injury. Subsequently, our laboratory embarked on the study of hypoxia tolerance using a mutagenesis and overexpression screens to begin to investigate loss-of-function or gain-of-function phenotypes. Both have given us promising results and, in this article, we detail some of the interesting results. Furthermore, several years ago, we have also started an experimental "Darwinian" selection to generate a fly strain that can perpetuate through all of its life cycle stages in hypoxic environments. Through microarrays and bioinformatic analyses, we have obtained genes (e.g. Notch pathway genes) that play an important role in hypoxia resistance. In addition, we also detail a proof of principle that Drosophila genes that are beneficial in fly resistance to hypoxia can also be as well in mammalian cells. We believe that the mechanisms that we are uncovering in Drosophila will allow us to gain insight regarding susceptibility and tolerance to low O2 and will therefore pave the way to develop better therapies for ailments that afflict humans as a consequence of low O2 delivery or low blood O2 levels.
Zhou
Dan
D
Department of Pediatrics, University of California, San Diego, California 92093, USA.
Visk
Deeann W
DW
Haddad
Gabriel G
GG
D000222:Adaptation, Physiological / Q000235:genetics*; D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D005821:Genetic Techniques; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D023421:Models, Animal; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D010641:Phenotype; D016601:RNA-Binding Proteins; D015398:Signal Transduction / Q000502:physiology
D000243:Adenosine Deaminase; D029721:Drosophila Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010100:Oxygen; D016601:RNA-Binding Proteins; C520727:MRP4 protein, Drosophila; C567955:ADARB1 protein, human