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Gene Review

Rdl  -  Resistant to dieldrin

Drosophila melanogaster

Synonyms: CG10537, CT29555, DmRDL, DmRdl, Dmel\CG10537, ...
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Disease relevance of Rdl

  • Recombinant baculoviruses containing two alternative splice forms of the Drosophila Rdl GABA receptor gene were constructed [1].
  • In order to examine the conservation of the mechanism of cyclodiene insecticide resistance between species we cloned a cDNA from the yellow fever mosquito Aedes aegypti homologous to the resistance gene Rdl in Drosophila [2].
  • Thus, the selective toxicity of fipronil and fipronil-derived residues is due in part to the higher potency of the parent compound at the insect versus the mammalian GABA receptor but is also dependent on the relative rates of conversion to the more persistent and less selective sulfone metabolite and desulfinyl photoproduct [3].
  • Properties of GABA-induced current in cultured CNS (ganglion) neurons of cutworm moths (Spodoptera litura) were studied using a whole-cell patch-clamp technique [4].

Psychiatry related information on Rdl

  • Recovery of normal locomotor activity and the righting reflex in DABA- and NipA-treated flies was achieved by coadministration of bicuculline (BIC), a GABA receptor antagonist that supresses GABAergic activity in mammals [5].
  • A missense mutation has been found in the gene encoding the GABA-A beta 3 subunit in a patient with chronic insomnia [6].
  • However, the properties of GABAergic neurons and the cellular effects of GABA have not been described in Drosophila, an important model organism for olfaction research [7].

High impact information on Rdl

  • Subsequently, genetic analysis and metabolite profiling confirmed a complex role for ornithine and GABA levels in modification of survival time upon chronic nicotine exposure [8].
  • GABAA receptors in vertebrates assemble as heteromultimers to form an integral chloride ion channel [9].
  • A point mutation in a Drosophila GABA receptor confers insecticide resistance [9].
  • Picrotoxinin (PTX) and cyclodiene insecticides are GABAA receptor antagonists which competitively displace each other from the same binding site [9].
  • This mutation not only identifies a single amino acid conferring high levels of resistance to the important GABA receptor antagonist PTX but also, by conferring resistance to cyclodienes, may account for over 60% of reported cases of insecticide resistance [9].

Biological context of Rdl


Anatomical context of Rdl


Associations of Rdl with chemical compounds

  • Drosophila gamma-aminobutyric acid receptor gene Rdl shows extensive alternative splicing [10].
  • Rdl codes for a subunit of a novel class of GABA gated chloride ion channels and resistance is correlated with replacement of the same amino acid residue in a wide range of species from different insect orders [17].
  • Pentobarbitone greatly enhances GABA-evoked currents, whereas the neurosteroid 5 alpha-pregnan-3 alpha-ol-20-one demonstrates a large reduction in both the potency and maximal effect when compared with its actions upon vertebrate GABA type A receptors [13].
  • Of the four receptor variants tested, the double mutant showed the highest resistance to fipronil, following repeated GABA applications [18].
  • In addition to providing a possible physiological role for the alternative splicing of Rdl, these data delineate a hitherto functionally unassigned region of the N-terminal domain of GABA receptor subunits, which affects agonist potency and aligns closely with known determinants of potency in nicotinic acetylcholine receptors [19].

Other interactions of Rdl

  • Interestingly, despite the complexity of the encoded receptors or enzymes, very few amino acid residues are replaced in different resistant insects: one within RDL, two within PARA and three or more within AChE [20].
  • In addition, we demonstrated a direct correlation between the amount of dFmrp and the expression of the GABA receptor subunits Rdl and Grd [21].
  • Mutation of the human beta3 subunit asparagine to methionine (beta3 N289M found in the equivalent position in Rdl completely inhibited both the GABA-modulatory and GABA-mimetic action of etomidate (10-300 microM) acting at alpha6beta3 N289Mgamma2L receptors [22].
  • It has been shown that DBI and its processing products are involved in various specific biological processes such as GABAA/benzodiazepine receptor modulation, acyl coenzyme A metabolism, steroidogenesis, and insulin secretion [23].
  • This approach yielded three discrete amplified sequence elements (designated LCCH1, LCCH2, and LCCH3) that contained open reading frames and > 40% amino acid sequence identity to the corresponding regions of vertebrate ligand-gated chloride channel genes [24].

Analytical, diagnostic and therapeutic context of Rdl

  • Molecular cloning of the cDNA encoding the RDL GABA receptor subunit of this strain revealed the presence of two mutations: the Rdl mutation (A301G) and an additional mutation in the third transmembrane domain (T350M) [18].
  • Genomic clones from the Rdl locus of Drosophila, whose mutant phenotype is resistant to cyclodiene insecticides and picrotoxin, were characterized by restriction mapping and partial sequencing to determine intron/exon structure [25].
  • Detailed immunocytochemistry of Drosophila brain sections showed particularly strong anti-Rdl antibody staining in the optic lobes, ellipsoid body, fan shaped body, ventrolateral protocerebrum and the glomeruli of the antennal lobes [26].
  • In situ hybridization using Rdl cDNA probes and the anti-Rdl antibody shows that Rdl message and protein are highly expressed in the developing central nervous system (CNS) of 15-17 h embryos [26].
  • We confirmed such GABA control mechanisms in an independent model system, i.e. primary Drosophila cell cultures raised in elevated [K+] [27].


  1. Expression of a Drosophila GABA receptor in a baculovirus insect cell system. Functional expression of insecticide susceptible and resistant GABA receptors from the cyclodiene resistance gene Rdl. Lee, H.J., Rocheleau, T., Zhang, H.G., Jackson, M.B., ffrench-Constant, R.H. FEBS Lett. (1993) [Pubmed]
  2. Cloning and sequencing of the cyclodiene insecticide resistance gene from the yellow fever mosquito Aedes aegypti. Conservation of the gene and resistance associated mutation with Drosophila. Thompson, M., Shotkoski, F., ffrench-Constant, R. FEBS Lett. (1993) [Pubmed]
  3. Mechanisms for selective toxicity of fipronil insecticide and its sulfone metabolite and desulfinyl photoproduct. Hainzl, D., Cole, L.M., Casida, J.E. Chem. Res. Toxicol. (1998) [Pubmed]
  4. Preliminary analysis of the GABA-induced current in cultured CNS neurons of the cutworm moth, Spodoptera litura. Satoh, H., Daido, H., Nakamura, T. Neurosci. Lett. (2005) [Pubmed]
  5. Pharmacological evidence for GABAergic regulation of specific behaviors in Drosophila melanogaster. Leal, S.M., Neckameyer, W.S. J. Neurobiol. (2002) [Pubmed]
  6. Genetics of the sleep-wake cycle and its disorders. Hamet, P., Tremblay, J. Metab. Clin. Exp. (2006) [Pubmed]
  7. Role of GABAergic inhibition in shaping odor-evoked spatiotemporal patterns in the Drosophila antennal lobe. Wilson, R.I., Laurent, G. J. Neurosci. (2005) [Pubmed]
  8. Quantitative trait transcripts for nicotine resistance in Drosophila melanogaster. Passador-Gurgel, G., Hsieh, W.P., Hunt, P., Deighton, N., Gibson, G. Nat. Genet. (2007) [Pubmed]
  9. A point mutation in a Drosophila GABA receptor confers insecticide resistance. Ffrench-Constant, R.H., Rocheleau, T.A., Steichen, J.C., Chalmers, A.E. Nature (1993) [Pubmed]
  10. Drosophila gamma-aminobutyric acid receptor gene Rdl shows extensive alternative splicing. ffrench-Constant, R.H., Rocheleau, T.A. J. Neurochem. (1993) [Pubmed]
  11. GABA receptors containing Rdl subunits mediate fast inhibitory synaptic transmission in Drosophila neurons. Lee, D., Su, H., O'Dowd, D.K. J. Neurosci. (2003) [Pubmed]
  12. Molecular cloning and transformation of cyclodiene resistance in Drosophila: an invertebrate gamma-aminobutyric acid subtype A receptor locus. Ffrench-Constant, R.H., Mortlock, D.P., Shaffer, C.D., MacIntyre, R.J., Roush, R.T. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  13. Cloning and functional expression of a Drosophila gamma-aminobutyric acid receptor. Chen, R., Belelli, D., Lambert, J.J., Peters, J.A., Reyes, A., Lan, N.C. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  14. Stable expression of a functional homo-oligomeric Drosophila GABA receptor in a Drosophila cell line. Millar, N.S., Buckingham, S.D., Sattelle, D.B. Proc. Biol. Sci. (1994) [Pubmed]
  15. Transcriptional analysis of the Drosophila GABA receptor gene resistance to dieldrin. Stilwell, G.E., ffrench-Constant, R.H. J. Neurobiol. (1998) [Pubmed]
  16. Distribution of two GABA receptor-like subunits in the Drosophila CNS. Aronstein, K., Auld, V., Ffrench-Constant, R. Invert. Neurosci. (1996) [Pubmed]
  17. The molecular and population genetics of cyclodiene insecticide resistance. Ffrench-Constant, R.H. Insect Biochem. Mol. Biol. (1994) [Pubmed]
  18. Resistance to fipronil in Drosophila simulans: influence of two point mutations in the RDL GABA receptor subunit. Le Goff, G., Hamon, A., Bergé, J.B., Amichot, M. J. Neurochem. (2005) [Pubmed]
  19. Alternative splicing of a Drosophila GABA receptor subunit gene identifies determinants of agonist potency. Hosie, A.M., Buckingham, S.D., Presnail, J.K., Sattelle, D.B. Neuroscience (2001) [Pubmed]
  20. Why are there so few resistance-associated mutations in insecticide target genes? ffrench-Constant, R.H., Pittendrigh, B., Vaughan, A., Anthony, N. Philos. Trans. R. Soc. Lond., B, Biol. Sci. (1998) [Pubmed]
  21. Decreased expression of the GABA(A) receptor in fragile X syndrome. D'Hulst, C., De Geest, N., Reeve, S.P., Van Dam, D., De Deyn, P.P., Hassan, B.A., Kooy, R.F. Brain Res. (2006) [Pubmed]
  22. The effect of a transmembrane amino acid on etomidate sensitivity of an invertebrate GABA receptor. McGurk, K.A., Pistis, M., Belelli, D., Hope, A.G., Lambert, J.J. Br. J. Pharmacol. (1998) [Pubmed]
  23. Tissue-specific expression of the diazepam-binding inhibitor in Drosophila melanogaster: cloning, structure, and localization of the gene. Kolmer, M., Roos, C., Tirronen, M., Myöhänen, S., Alho, H. Mol. Cell. Biol. (1994) [Pubmed]
  24. PCR-based homology probing reveals a family of GABA receptor-like genes in Drosophila melanogaster. Henderson, J.E., Knipple, D.C., Soderlund, D.M. Insect Biochem. Mol. Biol. (1994) [Pubmed]
  25. Drosophila cyclodiene resistance gene shows conserved genomic organization with vertebrate gamma-aminobutyric acidA receptors. ffrench-Constant, R.H., Rocheleau, T. J. Neurochem. (1992) [Pubmed]
  26. Immunocytochemistry of a novel GABA receptor subunit Rdl in Drosophila melanogaster. Aronstein, K., Ffrench-Constant, R. Invert. Neurosci. (1995) [Pubmed]
  27. In developing Drosophila neurones the production of gamma-amino butyric acid is tightly regulated downstream of glutamate decarboxylase translation and can be influenced by calcium. Küppers, B., Sánchez-Soriano, N., Letzkus, J., Technau, G.M., Prokop, A. J. Neurochem. (2003) [Pubmed]
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