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Gene Review

tko  -  technical knockout

Drosophila melanogaster

Synonyms: 40S ribosomal protein S12, mitochondrial, CG7925, Dmel\CG7925, EG:BACH59J11.1, MRP-S12, ...
 
 
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Disease relevance of tko

  • 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 [1].
  • The Drosophila mutant technical knockout (tko), affecting the mitochondrial protein synthetic apparatus, exhibits respiratory chain deficiency and a phenotype resembling various features of mitochondrial disease in humans (paralytic seizures, deafness, developmental retardation) [2].
  • We have used the E. coli gene to model the phenotypic effects of specific substitutions found in the mitochondrial gene for rps12 [3].
 

High impact information on tko

  • We suggest that tko codes for a mitochondrial ribosomal protein and that the tko phenotype results from defective mitochondria [4].
  • Our ultrastructural analysis reveals that these ribosomes include both mitochondrial rRNAs and at least two mitochondrial ribosomal proteins (S12 and L7/L12) [5].
  • A substitution with respect to eubacterial rps12 (K87-->Q), found in all metazoan and fungal mitochondrial orthologues thus far studied, is associated with low-level resistance to streptomycin and a modest (15%) drop in translational elongation rate, but without significant effects on translational accuracy [3].
  • These results indicate novel structure-function relationships in rps12 genes affecting translational function, ribosome assembly and drug sensitivity, and indicate a novel regulatory pathway that may influence ribosome biogenesis [3].
  • Restriction-map variation at the zeste-tko region in natural populations of Drosophila melanogaster [6].
 

Biological context of tko

  • DNA sequence analysis of tko and eas has indicated that they encode apparently unrelated biochemical products [7].
  • Restriction-map variation in 64 X chromosome lines extracted from three different natural populations of Drosophila melanogaster was investigated with seven six-nucleotide-recognizing enzymes for a 20-kb region including the zeste and tko genes [6].
  • Inbreeding of tko mutant lines results in a systematic improvement in all phenotypic parameters tested [2].
 

Other interactions of tko

  • Seizures caused by easily shocked (eas) and technical knockout (tko) mutations are partially suppressed by shakB2 [8].
 

Analytical, diagnostic and therapeutic context of tko

References

  1. Technical knockout, a Drosophila model of mitochondrial deafness. Toivonen, J.M., O'Dell, K.M., Petit, N., Irvine, S.C., Knight, G.K., Lehtonen, M., Longmuir, M., Luoto, K., Touraille, S., Wang, Z., Alziari, S., Shah, Z.H., Jacobs, H.T. Genetics (2001) [Pubmed]
  2. Mitochondrial disease in flies. Jacobs, H.T., Fernández-Ayala, D.J., Manjiry, S., Kemppainen, E., Toivonen, J.M., O'Dell, K.M. Biochim. Biophys. Acta (2004) [Pubmed]
  3. Modelling in Escherichia coli of mutations in mitoribosomal protein S12: novel mutant phenotypes of rpsL. Toivonen, J.M., Boocock, M.R., Jacobs, H.T. Mol. Microbiol. (1999) [Pubmed]
  4. The tko locus, site of a behavioral mutation in D. melanogaster, codes for a protein homologous to prokaryotic ribosomal protein S12. Royden, C.S., Pirrotta, V., Jan, L.Y. Cell (1987) [Pubmed]
  5. Presence of mitochondria-type ribosomes outside mitochondria in germ plasm of Drosophila embryos. Amikura, R., Kashikawa, M., Nakamura, A., Kobayashi, S. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  6. Restriction-map variation at the zeste-tko region in natural populations of Drosophila melanogaster. Aguadé, M., Miyashita, N., Langley, C.H. Mol. Biol. Evol. (1989) [Pubmed]
  7. Altered mechanoreceptor response in Drosophila bang-sensitive mutants. Engel, J.E., Wu, C.F. J. Comp. Physiol. A (1994) [Pubmed]
  8. Seizure suppression by shakB2, a gap junction mutation in Drosophila. Song, J., Tanouye, M.A. J. Neurophysiol. (2006) [Pubmed]
 
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