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To develop animal models of such disorders, we have manipulated the nuclear gene for mitochondrial ribosomal protein S12 in Drosophila (technical knockout, tko). The prototypic mutant tko25t exhibits developmental delay, bang sensitivity, impaired male courtship, and defective response to sound. On the basis of a transgenic reversion test, these phenotypes are attributable to a single substitution (L85H) at a conserved residue of the tko protein. The mutant is hypersensitive to doxycyclin, an antibiotic that selectively inhibits mitochondrial protein synthesis, and mutant larvae have greatly diminished activities of mitochondrial redox enzymes and decreased levels of mitochondrial small-subunit rRNA. A second mutation in the tko gene, Q116K, which is predicted to impair the accuracy of mitochondrial translation, results in the completely different phenotype of recessive female sterility, based on three independent transgenic insertions. We infer that the tko25t mutant provides a model of mitochondrial hearing impairment resulting from a quantitative deficiency of mitochondrial translational capacity.<\/jats:p>","DOI":"10.1093\/genetics\/159.1.241","type":"journal-article","created":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T04:19:32Z","timestamp":1619583572000},"page":"241-254","source":"Crossref","is-referenced-by-count":89,"title":["<i>technical knockout<\/i>, a Drosophila Model of Mitochondrial Deafness"],"prefix":"10.1093","volume":"159","author":[{"given":"Janne M","family":"Toivonen","sequence":"first","affiliation":[{"name":"Institute of Medical Technology & Tampere University Hospital, FIN-33014 University of Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin M C","family":"O'Dell","sequence":"additional","affiliation":[{"name":"IBLS Division of Molecular Genetics, University of Glasgow, Glasgow G11 6NU, Scotland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Petit","sequence":"additional","affiliation":[{"name":"UMR CNRS 6547, Equipe G\u00e9nome Mitochondrial, Universit\u00e9 Blaise Pascal, 63177 Aubi\u00e8re Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon C","family":"Irvine","sequence":"additional","affiliation":[{"name":"IBLS Division of Molecular Genetics, University of Glasgow, Glasgow G11 6NU, Scotland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian K","family":"Knight","sequence":"additional","affiliation":[{"name":"IBLS Division of Molecular Genetics, University of Glasgow, Glasgow G11 6NU, Scotland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjo","family":"Lehtonen","sequence":"additional","affiliation":[{"name":"Institute of Medical Technology & Tampere University Hospital, FIN-33014 University of Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Longmuir","sequence":"additional","affiliation":[{"name":"Institute of Medical Technology & Tampere University Hospital, FIN-33014 University of Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaisa","family":"Luoto","sequence":"additional","affiliation":[{"name":"Institute of Medical Technology & Tampere University Hospital, FIN-33014 University of Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Touraille","sequence":"additional","affiliation":[{"name":"UMR CNRS 6547, Equipe G\u00e9nome Mitochondrial, Universit\u00e9 Blaise Pascal, 63177 Aubi\u00e8re Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongsheng","family":"Wang","sequence":"additional","affiliation":[{"name":"IBLS Division of Molecular Genetics, University of Glasgow, Glasgow G11 6NU, Scotland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Alziari","sequence":"additional","affiliation":[{"name":"UMR CNRS 6547, Equipe G\u00e9nome Mitochondrial, Universit\u00e9 Blaise Pascal, 63177 Aubi\u00e8re Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahid H","family":"Shah","sequence":"additional","affiliation":[{"name":"Institute of Medical Technology & Tampere University Hospital, FIN-33014 University of Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard T","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Institute of Medical Technology & Tampere University Hospital, FIN-33014 University of Tampere, Finland"},{"name":"IBLS Division of Molecular Genetics, University of Glasgow, Glasgow G11 6NU, Scotland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2001,9,1]]},"reference":[{"key":"2022010507051818000_R1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0006-291X(81)91704-6","article-title":"In vitro incorporation of [35S]methionine in mitochondrial proteins of Drosophila melanogaster","volume":"99","author":"Alziari","year":"1981","journal-title":"Biochem. 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