title: Gene dosage and selective expression modify phenotype in a Drosophila model of human mitochondrial disease.
abstract: Human mitochondrial disease manifests with a wide range of clinical phenotypes of varying severity. To create a model for these disorders, we have manipulated the Drosophila gene technical knockout, encoding mitoribosomal protein S12. Various permutations of endogenous and transgenic alleles create a range of phenotypes, varying from larval developmental arrest through to mild neurological defects in the adult, and also mimic threshold effects associated with human mtDNA disease. Nuclear genetic background influences mutant phenotype by a compensatory mechanism affecting mitochondrial RNA levels. Selective expression of the wild-type allele indicates critical times and cell-types in development, in which mitochondrial protein synthesis deficiency leads to specific phenotypic outcomes.
authors.affiliation: Institute of Medical Technology and Tampere University Hospital, 33014 Tampere, Finland.
authors.forename: Janne M
authors.initials: JM
authors.lastname: Toivonen
authors.forename: Shweta
authors.initials: S
authors.lastname: Manjiry
authors.forename: Sylvie
authors.initials: S
authors.lastname: Touraille
authors.forename: Serge
authors.initials: S
authors.lastname: Alziari
authors.forename: Kevin M C
authors.initials: KM
authors.lastname: O'Dell
authors.forename: Howard T
authors.initials: HT
authors.lastname: Jacobs