g

Summary

Gene Symbol: g
Description: garnet
Alias: AP-3delta, AP3delta, CG10986, CG11197, Dmel\CG10986, apl5, cg11197, delta, l(1)Mc19, garnet, AP-3, delta subunit, CG10986-PB, CG10986-PD, CG10986-PF, adaptor protein complex 3, delta subunit, g-PB, g-PD, g-PF, lethal(1)Mc19, salmon
Species: fruit fly

Top Publications

  1. Hardy R, Lindsley D, Livak K, Lewis B, Siversten A, Joslyn G, et al. Cytogenetic analysis of a segment of the Y chromosome of Drosophila melanogaster. Genetics. 1984;107:591-610 pubmed
    ..The meiotic phenotype is apparently sensitive to the amount of Y chromosome missing and to the Ste constitution of the X chromosome. ..
  2. Cardnell R, Nogare D, Ganetzky B, Stern M. In vivo analysis of a gain-of-function mutation in the Drosophila eag-encoded K+ channel. Genetics. 2006;172:2351-8 pubmed
    ..We hypothesize that the G297E substitution may cause premature, prolonged, or constitutive opening of the Eag channels by favoring the "unlocked" state of the channel. ..
  3. Anaka M, Lynn A, McGinn P, Lloyd V. Genomic imprinting in Drosophila has properties of both mammalian and insect imprinting. Dev Genes Evol. 2009;219:59-66 pubmed publisher
  4. Ma J, Plesken H, Treisman J, Edelman Novemsky I, Ren M. Lightoid and Claret: a rab GTPase and its putative guanine nucleotide exchange factor in biogenesis of Drosophila eye pigment granules. Proc Natl Acad Sci U S A. 2004;101:11652-7 pubmed
    ..that the gene products of claret and lightoid function in the same pathway, which is different from that of garnet and ruby (which encode the delta- and beta-subunit of the tetrameric adaptor protein 3 complex, respectively)...
  5. Boehm M, Bonifacino J. Adaptins: the final recount. Mol Biol Cell. 2001;12:2907-20 pubmed
    ..Finally, we extend our survey to adaptin-related proteins such as the GGAs and stonins, which contain domains homologous to the adaptins. ..
  6. Ooi C, Moreira J, Dell Angelica E, Poy G, Wassarman D, Bonifacino J. Altered expression of a novel adaptin leads to defective pigment granule biogenesis in the Drosophila eye color mutant garnet. EMBO J. 1997;16:4508-18 pubmed
    ..We report here that a defect in a gene encoding a putative coat adaptor protein leads to the eye color defect of garnet mutants...
  7. Falcon Perez J, Romero Calderon R, Brooks E, Krantz D, Dell Angelica E. The Drosophila pigmentation gene pink (p) encodes a homologue of human Hermansky-Pudlak syndrome 5 (HPS5). Traffic. 2007;8:154-68 pubmed
    ..The phenotype of pink mutants was exacerbated by mutations in AP-3 subunits or in the orthologs of VPS33A and Rab38. These results validate D. melanogaster as a genetic model to study the function of the BLOCs. ..
  8. Kondylis V, Goulding S, Dunne J, Rabouille C. Biogenesis of Golgi stacks in imaginal discs of Drosophila melanogaster. Mol Biol Cell. 2001;12:2308-27 pubmed
    ..Taken together, these results suggest that we have developed an in vivo system to study the ecdysone-triggered Golgi stack biogenesis. ..
  9. Lloyd V, Sinclair D, Grigliatti T. Genomic imprinting and position-effect variegation in Drosophila melanogaster. Genetics. 1999;151:1503-16 pubmed
    ..This suggests that chromatin structure is important in maintenance of the imprint, but a separate mechanism may be responsible for its initiation. ..

More Information

Publications73

  1. Lloyd V, Ramaswami M, Kramer H. Not just pretty eyes: Drosophila eye-colour mutations and lysosomal delivery. Trends Cell Biol. 1998;8:257-9 pubmed
    ..Thus, classical work describing more than 85 eye-colour mutations and their genetic interactions offers a remarkable, untapped resource for the genetic analysis of protein delivery to lysosomes. ..
  2. Kulkarni S, Steinlauf A, Hall J. The dissonance mutant of courtship song in Drosophila melanogaster: isolation, behavior and cytogenetics. Genetics. 1988;118:267-85 pubmed
  3. Hayashi R, Handler D, Ish Horowicz D, Brennecke J. The exon junction complex is required for definition and excision of neighboring introns in Drosophila. Genes Dev. 2014;28:1772-85 pubmed publisher
    ..Based on a transcriptome-wide analysis, we propose that the dependency of splicing on the EJC is exploited as a means to control the temporal order of splicing events. ..
  4. Elias V, Nicolas C, Abramson C. Eye color as an indicator of behavior: revisiting Worthy and Scott. Psychol Rep. 2008;102:759-78 pubmed
    ..melanogaster pointed to significant behavioral differences among cell-defect groups, indicating that the cell defect which causes eye color, rather than eye color itself, may serve as a crude indicator of behavior. ..
  5. Aparisi M, Najera C. Genetic location and biochemical characterization of eye-colour mutants from natural populations of Drosophila melanogaster. Genome. 1990;33:203-8 pubmed
    ..The eye-colour mutants show large effects on the red and brown pigments. The high variability of the eye-colour loci is discussed in relation to the mutation and selection hypotheses. ..
  6. Georgiev P, Gerasimova T. Genes involved in the development of bristles and hairs in Drosophila melanogaster. Genetica. 1992;87:31-5 pubmed
    ..Mutations in the third gene, pseudoscute, lead to reduction of all bristles and hairs. The latter locus seems to control the development of bristles independently of the achaete-scute complex control. ..
  7. Asensio C, Sirkis D, Edwards R. RNAi screen identifies a role for adaptor protein AP-3 in sorting to the regulated secretory pathway. J Cell Biol. 2010;191:1173-87 pubmed publisher
    ..Although vesicles with a dense core still form in the absence of AP-3, they contain substantially less synaptotagmin 1, indicating that AP-3 concentrates the proteins required for regulated exocytosis. ..
  8. Daborn P, McKenzie J, Batterham P. A genetic analysis of cyromazine resistance in Drosophila melanogaster (Diptera: Drosophilidae). J Econ Entomol. 2000;93:911-9 pubmed
    ..This is possibly an allele of a previously characterized cyromazine resistance gene, Rst(2)Cyr. Dosage-mortality analyses demonstrate a low level of cyromazine resistance is conferred in all strains. ..
  9. Rodriguez Fernandez I, Dell Angelica E. Identification of Atg2 and ArfGAP1 as Candidate Genetic Modifiers of the Eye Pigmentation Phenotype of Adaptor Protein-3 (AP-3) Mutants in Drosophila melanogaster. PLoS ONE. 2015;10:e0143026 pubmed publisher
    ..These results provide genetic evidence for new functional links connecting the machinery for biogenesis of LROs with molecules implicated in autophagy and small GTPase regulation. ..
  10. Perrimon N, Gans M. Clonal analysis of the tissue specificity of recessive female-sterile mutations of Drosophila melanogaster using a dominant female-sterile mutation Fs(1)K1237. Dev Biol. 1983;100:365-73 pubmed
    ..These results are discussed in terms of a coincident production of clones in the follicle cells. ..
  11. Barbosa V, Yamamoto R, Henderson D, Glover D. Mutation of a Drosophila gamma tubulin ring complex subunit encoded by discs degenerate-4 differentially disrupts centrosomal protein localization. Genes Dev. 2000;14:3126-39 pubmed
    ..This suggests that in addition to its role in nucleating cytoplasmic and spindle microtubules, the gammaTuRC is also essential to the structure of centrioles and the separation of centrosomes. ..
  12. Haigh A, Lloyd V. Why clone flies? Using cloned Drosophila to monitor epigenetic defects. Fly (Austin). 2007;1:6-12 pubmed
    ..Thus, Drosophila can potentially be used to study epigenetic dysfunction in cloned animals and to screen for genetic and epigenetic conditions that promote the production of healthy clones. ..
  13. Beadle G. Development of Eye Colors in Drosophila: Fat Bodies and Malpighian Tubes in Relation to Diffusible Substances. Genetics. 1937;22:587-611 pubmed
  14. Warner T, Sinclair D, Fitzpatrick K, Singh M, Devlin R, Honda B. The light gene of Drosophila melanogaster encodes a homologue of VPS41, a yeast gene involved in cellular-protein trafficking. Genome. 1998;41:236-43 pubmed
    ..alleles of lt and dor, as well as phenotypic interactions (reductions in eye pigment) between allels of lt and another eye-colour gene, garnet (g), whose gene product has close homology to a subunit of the human adaptor complex, AP-3.
  15. Ganetzky B, Wu C. Indirect Suppression Involving Behavioral Mutants with Altered Nerve Excitability in DROSOPHILA MELANOGASTER. Genetics. 1982;100:597-614 pubmed
    ..Genetic interactions of this type help reveal functional relationships between different behavioral mutants and suggest ways of isolating new mutants with altered excitable membranes. ..
  16. Deak I, Bellamy P, Bienz M, Dubuis Y, Fenner E, Gollin M, et al. Mutations affecting the indirect flight muscles of Drosophila melanogaster. J Embryol Exp Morphol. 1982;69:61-81 pubmed
    ..b>g. aberrant or missing Z-bands, or absence of the thin filaments...
  17. Lloyd V. Parental imprinting in Drosophila. Genetica. 2000;109:35-44 pubmed
    ..Thus, the study of imprinting in Drosophila has the potential to illuminate the mechanism and biological function of imprinting, and challenge models based solely on imprinting of mammalian genes. ..
  18. Mullins C, Hartnell L, Bonifacino J. Distinct requirements for the AP-3 adaptor complex in pigment granule and synaptic vesicle biogenesis in Drosophila melanogaster. Mol Gen Genet. 2000;263:1003-14 pubmed
    ..Together, these results demonstrate that Drosophila AP-3 is critical for the biogenesis of pigment granules, but is apparently not essential for formation of a major population of synaptic vesicles in vivo. ..
  19. Beadle G, Ephrussi B. The Differentiation of Eye Pigments in Drosophila as Studied by Transplantation. Genetics. 1936;21:225-47 pubmed
  20. Hall J. Courtship lite: a personal history of reproductive behavioral neurogenetics in Drosophila. J Neurogenet. 2002;16:135-63 pubmed
  21. Ruiz Vázquez P, Silva F, Ferre J. Characterization of sepiapterin reductase activity from Drosophila melanogaster. Comp Biochem Physiol B Biochem Mol Biol. 1996;113:131-6 pubmed
    ..0. A study of the activity in different eye-color mutant strains revealed significantly decreased levels in clot, red Malpighian tubules and garnet.
  22. Christis C, Munro S. The small G protein Arl1 directs the trans-Golgi-specific targeting of the Arf1 exchange factors BIG1 and BIG2. J Cell Biol. 2012;196:327-35 pubmed publisher
    The small G protein Arf1 regulates Golgi traffic and is activated by two related types of guanine nucleotide exchange factor (GEF). GBF1 acts at the cis-Golgi, whereas BIG1 and its close paralog BIG2 act at the trans-Golgi...
  23. Wilkin M, Tongngok P, Gensch N, Clemence S, Motoki M, Yamada K, et al. Drosophila HOPS and AP-3 complex genes are required for a Deltex-regulated activation of notch in the endosomal trafficking pathway. Dev Cell. 2008;15:762-72 pubmed publisher
    ..We discuss ways in which these endocytic pathways may modulate ligand-dependent and -independent events, as a mechanism that can potentiate Notch signaling or dampen noise in the signaling network. ..
  24. Oh C, McMahon R, Benzer S, Tanouye M. bendless, a Drosophila gene affecting neuronal connectivity, encodes a ubiquitin-conjugating enzyme homolog. J Neurosci. 1994;14:3166-79 pubmed
    ..The major role of ubiquitination in the protein degradative pathway suggests that ben regulates neural developmental processes such as growth cone guidance by targeting specific proteins for degradation. ..
  25. Krishnan K, Nash H. A genetic study of the anesthetic response: mutants of Drosophila melanogaster altered in sensitivity to halothane. Proc Natl Acad Sci U S A. 1990;87:8632-6 pubmed
    ..In the absence of anesthetics, these mutants display alterations of behavior that imply changes in the adult and the larval neuromuscular system. ..
  26. Rikhy R, Ramaswami M, Krishnan K. A temperature-sensitive allele of Drosophila sesB reveals acute functions for the mitochondrial adenine nucleotide translocase in synaptic transmission and dynamin regulation. Genetics. 2003;165:1243-53 pubmed
  27. Sorsa V, Green M, Beermann W. Cytogenetic fine structure and chromosomal localization of the white gene in Drosophila melanogaster. Nat New Biol. 1973;245:34-7 pubmed
  28. Muralidhar M, Thomas J. The Drosophila bendless gene encodes a neural protein related to ubiquitin-conjugating enzymes. Neuron. 1993;11:253-66 pubmed
    ..These results suggest a role for ubiquitin-mediated protein modification in nervous system development, including, but not exclusive to, the regulation of synaptic connectivity. ..
  29. Lloyd V, Sinclair D, Wennberg R, Warner T, Honda B, Grigliatti T. A genetic and molecular characterization of the garnet gene of Drosophila melanogaster. Genome. 1999;42:1183-93 pubmed
    The garnet gene was one of the first genes to be identified in Drosophila melanogaster. Mutations in the garnet gene affect both of the biochemically distinct types of pigments in the eye and disrupt pigmentation of other organs...
  30. Muraro N, Moffat K. Down-regulation of torp4a, encoding the Drosophila homologue of torsinA, results in increased neuronal degeneration. J Neurobiol. 2006;66:1338-53 pubmed
  31. Luzio J, Rous B, Bright N, Pryor P, Mullock B, Piper R. Lysosome-endosome fusion and lysosome biogenesis. J Cell Sci. 2000;113 ( Pt 9):1515-24 pubmed
  32. Benevolenskaya E, Frolov M, Birchler J. Krüppel homolog (Kr h) is a dosage-dependent modifier of gene expression in Drosophila. Genet Res. 2000;75:137-42 pubmed
    ..Genetic analysis of different white alleles suggests that enhancer sequences are necessary for interaction with KR H. Thus, the Kr h gene is a member of the dosage-dependent hierarchy effective upon white...
  33. Tearle R. Tissue specific effects of ommochrome pathway mutations in Drosophila melanogaster. Genet Res. 1991;57:257-66 pubmed
    ..Two mutations affecting the red eye pigments (drosopterins), bw and mal, do not substantially perturb brown pigment synthesis in any of the four organs. ..
  34. Mullins C, Bonifacino J. The molecular machinery for lysosome biogenesis. Bioessays. 2001;23:333-43 pubmed
    ..Other recently identified components, however, appear to be unique to higher eukaryotes. BioEssays 23:333-343, 2001. Published 2001 John Wiley & Sons, Inc. ..
  35. Cook R, Deal M, Deal J, Garton R, Brown C, Ward M, et al. A new resource for characterizing X-linked genes in Drosophila melanogaster: systematic coverage and subdivision of the X chromosome with nested, Y-linked duplications. Genetics. 2010;186:1095-109 pubmed publisher
    ..These duplication chromosomes will be valuable resources for rescuing and mapping X-linked mutations and identifying dosage-dependent modifiers of mutant phenotypes. ..
  36. MacDonald W, Menon D, Bartlett N, Sperry G, Rasheva V, MELLER V, et al. The Drosophila homolog of the mammalian imprint regulator, CTCF, maintains the maternal genomic imprint in Drosophila melanogaster. BMC Biol. 2010;8:105 pubmed publisher
    ..See commentary: http://www.biomedcentral.com/1741-7007/8/104. ..
  37. Spritz R. Multi-organellar disorders of pigmentation: intracellular traffic jams in mammals, flies and yeast. Trends Genet. 1999;15:337-40 pubmed
    ..Recent discoveries show that several of these mutations directly affect components in the pathway of organelle-specific protein trafficking, and provide new insights into the relationships of these pathways in mammals, flies and yeast. ..
  38. Saint R, Patterson B. Zygotic transcription and cell proliferation during Drosophila embryogenesis. Genetica. 1993;90:157-63 pubmed
    ..Genes that comprise the first class are involved in the developmental control of the cell cycle, while those of the second class identify components of the cell cycle machinery. ..
  39. Ripoll P. Behavior of somatic cells homozygous for zygotic lethals in Drosophila melanogaster. Genetics. 1977;86:357-76 pubmed
    ..The phenotypes at the cellular level of some cell-viable mutations altering cell parameters (mitotic orientation, differentiation, etc.) are described. ..
  40. Mason J, Green M, Shaw K, Boyd J. Genetic analysis of X-linked mutagen-sensitive mutants of Drosophila melanogaster. Mutat Res. 1981;81:329-43 pubmed
    ..Cytogenetically mus(1)101D1 is between salivary chromosome bands 12A6,7 and 12D3, mus(1)103D1 is between bands 12A1,2 and 12A6,7 and mus(1)109A1 is in section 8F3--9A2. ..
  41. Yamamoto R, Axton J, Yamamoto Y, Saunders R, Glover D, Henderson D. The Drosophila mus101 gene, which links DNA repair, replication and condensation of heterochromatin in mitosis, encodes a protein with seven BRCA1 C-terminus domains. Genetics. 2000;156:711-21 pubmed
    ..Mus101 also shares sequence similarity with the fission yeast Rad4/Cut5 protein required for repair, replication, and checkpoint control, suggesting that the two proteins may be functional homologs. ..
  42. Rodriguez Fernandez I, Dell Angelica E. A data-mining approach to rank candidate protein-binding partners-The case of biogenesis of lysosome-related organelles complex-1 (BLOC-1). J Inherit Metab Dis. 2009;32:190-203 pubmed publisher
    ..The data-mining approach described herein can be customized to study candidate binding partners for other proteins or possibly candidates derived from other types of 'omics' data. ..
  43. Cherry S, Perrimon N. Entry is a rate-limiting step for viral infection in a Drosophila melanogaster model of pathogenesis. Nat Immunol. 2004;5:81-7 pubmed
    ..Thus, this virus model provides a sensitive and efficient approach for identifying components required for pathogenesis. ..
  44. Slizynski B. Salivary Chromosome Studies of Lethals in Drosophila Melanogaster. Genetics. 1938;23:283-90 pubmed
  45. Kretzschmar D, Poeck B, Roth H, Ernst R, Keller A, Porsch M, et al. Defective pigment granule biogenesis and aberrant behavior caused by mutations in the Drosophila AP-3beta adaptin gene ruby. Genetics. 2000;155:213-23 pubmed
    ..Recently, eye and coat color mutations in mouse (mocha and pearl) and Drosophila (garnet and carmine) were shown to affect subunits of the heterotetrameric adaptor protein complex AP-3 involved in ..
  46. Swetha M, Sriram V, Krishnan K, Oorschot V, Ten Brink C, Klumperman J, et al. Lysosomal membrane protein composition, acidic pH and sterol content are regulated via a light-dependent pathway in metazoan cells. Traffic. 2011;12:1037-55 pubmed publisher
    ..Depletion of the mammalian counterpart of Light, hVps41, in a human cell line also inhibits delivery of hLAMP to endosomes, suggesting an evolutionarily conserved pathway in metazoa. ..
  47. Burgess J, Jauregui M, Tan J, Rollins J, Lallet S, Leventis P, et al. AP-1 and clathrin are essential for secretory granule biogenesis in Drosophila. Mol Biol Cell. 2011;22:2094-105 pubmed publisher
    ..Finally, loss of clathrin or AP-1 leads to a profound block in secretory granule formation. These findings establish a novel role for AP-1- and clathrin-dependent trafficking in the biogenesis of mucin-containing secretory granules. ..
  48. Burgess J, Del Bel L, Ma C, Barylko B, Polevoy G, Rollins J, et al. Type II phosphatidylinositol 4-kinase regulates trafficking of secretory granule proteins in Drosophila. Development. 2012;139:3040-50 pubmed publisher
    ..Our genetic analysis of PI4KII in flies thus reveals a novel role for PI4KII in regulating the fidelity of granule protein trafficking in secretory tissues. ..
  49. Silva F, Escriche B, Ordoño E, Ferre J. Genetic and biochemical characterization of little isoxanthopterin (lix), a gene controlling dihydropterin oxidase activity in Drosophila melanogaster. Mol Gen Genet. 1991;230:97-103 pubmed
    ..The activity was around 100% in most mutants tested, slightly reduced in red, g and dke, and undetectable in lix...
  50. Livingstone M. Genetic dissection of Drosophila adenylate cyclase. Proc Natl Acad Sci U S A. 1985;82:5992-6 pubmed
    ..The results suggest that the component of cyclase activity that is stimulated by calcium/calmodulin, possibly a genetically distinct catalytic subunit, is not coupled to the G subunit or the G subunit/monoamine receptor complex.
  51. Bridges C. Non-Disjunction as Proof of the Chromosome Theory of Heredity (Concluded). Genetics. 1916;1:107-63 pubmed
  52. Dell Angelica E, Mullins C, Caplan S, Bonifacino J. Lysosome-related organelles. FASEB J. 2000;14:1265-78 pubmed
  53. Singh N, Jensen J, Clark A, Aquadro C. Inferences of demography and selection in an African population of Drosophila melanogaster. Genetics. 2013;193:215-28 pubmed publisher
    ..0009. These inferences regarding the rate and strength of selection are largely consistent with most other estimates from D. melanogaster and indicate a relatively high rate of adaptation driven by weakly beneficial mutations. ..
  54. Chovnick A. The garnet locus in Drosophila melanogaster. I. Pseudoallelism. Genetics. 1961;46:493-507 pubmed
  55. Simpson F, Peden A, Christopoulou L, Robinson M. Characterization of the adaptor-related protein complex, AP-3. J Cell Biol. 1997;137:835-45 pubmed
    ..The delta subunit is closely related to the protein product of the Drosophila garnet gene, which when mutated results in reduced pigmentation of the eyes and other tissues...
  56. Vogt N, Koch I, Schwarz H, Schnorrer F, NUSSLEIN VOLHARD C. The gammaTuRC components Grip75 and Grip128 have an essential microtubule-anchoring function in the Drosophila germline. Development. 2006;133:3963-72 pubmed
    ..The gammaTuRC cap structure may be essential only for non-centrosome-based microtubule functions. ..
  57. Seong C, Kim Y, Chung H, Park D, Yim J, Baek K, et al. Isolation and characterization of the Drosophila melanogaster cDNA encoding the sepiapterin reductase. Biochim Biophys Acta. 1998;1443:239-44 pubmed
    ..Southern analysis suggests that the Drosophila SR gene is encoded by a single copy gene. RNA blot analysis revealed that the gene expresses 1.5 kb mRNA in both adult heads and bodies. ..
  58. Yampolsky L, Allen C, Shabalina S, Kondrashov A. Persistence time of loss-of-function mutations at nonessential loci affecting eye color in Drosophila melanogaster. Genetics. 2005;171:2133-8 pubmed
    ..In both cases, deleterious alleles are apparently eliminated by selection against heterozygous individuals, which show no visible phenotypic differences from wild type. ..
  59. Harris D, Kim K, Nakahara K, Vásquez Doorman C, Carthew R. Cargo sorting to lysosome-related organelles regulates siRNA-mediated gene silencing. J Cell Biol. 2011;194:77-87 pubmed publisher
    ..Negative regulation is also not linked to sorting into all LROs but only a specific class of pigment LRO. Thus, regulation of siRNA activity is tied to sorting of specific types of cargo to particular LROs...
  60. Wightman P, Jackson G, Dipple K. Glycerol hypersensitivity in a Drosophila model for glycerol kinase deficiency is affected by mutations in eye pigmentation genes. PLoS ONE. 2012;7:e31779 pubmed publisher
  61. Blumenthal E. Cloning of the neurodegeneration gene drop-dead and characterization of additional phenotypes of its mutation. Fly (Austin). 2008;2:180-8 pubmed
    ..This study demonstrates that mutation of the drd gene CG33968 results in a complex phenotype affecting multiple physiological systems within the fly. ..
  62. Singh N, Stone E, Aquadro C, Clark A. Fine-scale heterogeneity in crossover rate in the garnet-scalloped region of the Drosophila melanogaster X chromosome. Genetics. 2013;194:375-87 pubmed publisher
    ..Our results shed new light on the scale and magnitude of crossover rate heterogeneity in D. melanogaster and highlight potential features mediating this heterogeneity. ..
  63. Sturtevant A. Genetic Studies on DROSOPHILA SIMULANS. II. Sex-Linked Group of Genes. Genetics. 1921;6:43-64 pubmed
  64. Boehm M, Bonifacino J. Genetic analyses of adaptin function from yeast to mammals. Gene. 2002;286:175-86 pubmed
    ..Here, we review recent progress in the genetic analysis of the function of AP complexes, focusing on studies that make use of targeted interference or naturally-occurring mutations in various model organisms. ..