Table 1.
Genes that Influence Alcohol-Related Behavior in Flies
Gene (aka) | Function | Genetic manipulation | Behavioral assay | Measure | Effect | Citation |
---|---|---|---|---|---|---|
AcCoAS | Acetyl CoA synthesis | LOF mutant | Booz-o-mat | ACT | Decrease | Kong et al. (2010a) |
Adh | Alcohol dehydrogenase | LOF mutants | Booz-o-mat | % Sed | Increase | Wolf et al. (2002) |
LOF mutants | Unnamed | Locomotor activity | Decrease | Grell et al. (1968) | ||
LOF mutant | Inebriometer | MET, Rap Tol (MET) | Decrease | Cavener (1979) | ||
LOF mutant | Larval preference | Larvae on alcohol agar | Decrease | Ogueta et al. (2010) | ||
Akt1 (Akt) | Serine/threonine kinase | LOF mutant | Sedation | Time to Sed | Increase | Eddison et al. (2011) |
RNAi | Sedation | Time to Sed | Increase | |||
Overexpression | Sedation | Time to Sed | Decrease | |||
Alk | Receptor tyrosine kinase | LOF mutants | Booz-o-mat | Time to Sed | Increase | Lasek et al. (2011b) |
amn | PACAP-like neuropeptide | LOF mutants | Inebriometer | MET | Decrease | Moore et al. (1998) |
LOF mutants | Booz-o-mat | ACT, % Sed | Increase | Wolf et al. (2002) | ||
LOF mutant | Sedation | Time to Sed | Decrease | Peru Y Colon de Portugal et al. (2012) | ||
apt | Myb/SANT-containing transcription factor | LOF mutants | Sedation | Time to Sed | Increase | McClure and Heberlein (2013) |
RNAi | Sedation | Time to Sed | Increase | |||
Arf51F (Arf6) | Small G protein | LOF mutants | Sedation | Time to Sed | Decrease | Peru Y Colón de Portugal et al. (2012) |
Arfip | Dynactin binding | LOF mutant | Sedation | Time to Sed | Decrease | Peru Y Colón de Portugal et al. (2012) |
aru | Epidermal growth factor receptor substrate | LOF mutants | Inebriometer | MET, Time to Sed | Decrease | Eddison et al. (2011) |
LOF mutants | Sedation | MET, Time to Sed | Decrease | |||
RNAi | Inebriometer | MET, Time to Sed | Decrease | |||
RNAi | Sedation | MET, Time to Sed | Decrease | |||
Bacc | Ribosomal RNA-binding domain protein | LOF mutants | Sedation | Time to Sed | Increase | Chen et al. (2013) |
RNAi | Sedation | Time to Sed | Increase | |||
bsk | Serine–threonine kinase | LOF mutant | Booz-o-mat | ACT | Increase | Kapfhamer et al. (2012) |
Bx (dLmo) | Zinc-finger protein, LIM-type | LOF mutant | Sedation | Time to Sed | Decrease | Lasek et al. (2011a) |
GOF mutant | Sedation | Time to Sed | Increase | |||
CASK | Molecular scaffold | LOF mutants | Inebriometer | Rap Tol (MET) | Decrease | Maiya et al. (2012) |
Cdc42 | Small G protein | GOF transgenic | Sedation | % Sed | Increase | Rothenfluh et al. (2006) |
chico | Insulin receptor substrate | LOF mutant | Inebriometer | MET | Decrease | Corl et al. (2005) |
Clic | Numerous proposed | LOF mutants | eRING | Time to Sed | Increase | Bhandari et al. (2012) |
LOF mutants | Sedation | Time to Sed | Increase | Chan et al. (2014) | ||
RNAi | Sedation | Time to Sed | Increase | |||
Crz | Neuropeptide | RNAi | Sedation | Time to Sed | Increase | McClure and Heberlein (2013) |
LOF mutant | Sedation recovery | Time to Rec | Increase | Sha et al. (2014) | ||
CrzR | Corazonin receptor | RNAi | Sedation recovery | Time to Rec | Increase | Sha et al. (2014) |
cyc | Transcription factor | LOF mutant | Sedation | Rap Tol (Time to Sed) | Decrease | Pohl et al. (2013) |
Cyp1 | Peptidyl-prolyl cis-trans isomerase activity | RNAi | Inebriometer | MET | Increase | Morozova et al. (2011) |
dally | Glypican | LOF mutant | Video | ACT | Decrease | Joslyn et al. (2011) |
LOF mutant | Sedation | Time to Sed | Decrease | |||
DAT | Dopamine transporter | LOF mutant | Video | ACT | Decrease | Kong et al. (2010b) |
Overexpression | Video | ACT | Increase | |||
dlg1 | Membrane-associated guanylate kinase | LOF mutants | Inebriometer | Rap Tol, Chron Tol (MET) | Decrease | Maiya et al. (2012) |
dlp | Glypican | LOF mutant | Video | ACT | Decrease | Joslyn et al. (2011) |
LOF mutant | Sedation | Time to Sed | Decrease | |||
LOF mutant | Sedation | Rap Tol | Increase | |||
Dop1R1 | Dopamine receptor | LOF mutant | Video | ACT | Decrease | Bainton et al. (2000) |
LOF mutant | Video | ACT | Decrease | Kong et al. (2010b) | ||
Egfr | Epidermal growth factor receptor | Overexpression | Sedation | Time to Sed | Increase | Corl et al. (2009) |
RNAi, inhibitor | Sedation | Time to Sed | Decrease | |||
elm | P22 calcineurin B | LOF mutant | Inebriometer | MET | Decrease | LaFerriere et al. (2008) |
Fas2 | Ig-domain adhesion molecule | LOF mutants | Inebriometer | MET | Decrease | Cheng et al. (2001) |
Fng | UDP-glycosyltransferase | RNAi | Inebriometer | Rap Tol (MET) | Increase | Morozova et al. (2011) |
FOXO | Transcription factor | Overexpression | Inebriometer | MET | Decrease | Corl et al. (2005) |
Fs | Negative regulator of activin receptor signaling | GOF mutant | Inebriometer | MET | Increase | Morozova et al. (2011) |
GABA-B-R1 | Metabotropic GABA receptor | RNAi | Sedation recovery | Sed Rec Time | Decrease | Dzitoyeva et al. (2003) |
Antagonist | Sedation recovery | Sed Rec Time | Decrease | |||
Agonist | Sedation recovery | Rap Tol (Sed Rec Time) | Decrease | |||
H15 | T-box transcription factor | RNAi | Inebriometer | MET | Increase | Morozova et al. (2011) |
hang | Zinc-finger protein | LOF mutant | Inebriometer | Rap Tol (MET) | Decrease | Scholz et al. (2005) |
LOF mutant | eRING | Rap Tol (Time to Sed) | Decrease | Bhandari et al. (2009) | ||
homer | Postsynaptic scaffolding | LOF mutant | Sedation | Time to Sed | Decrease | Urizar et al. (2007) |
LOF mutant | Sedation | Rap Tol (Time to Sed) | Decrease | |||
hppy | Ste20 kinase | LOF mutants | Video, Sedation | Time to Sed | Increase | Corl et al. (2009) |
LOF mutant | Sedation | Time to Sed | Increase | Eddison et al. (2011) | ||
Hsp26 | Heat shock protein | Transposons | Sedation | Rap Tol (Time to Sed) | Decrease | Awofala et al. (2011) |
RNAi | Sedation | Rap Tol (Time to Sed) | Decrease | |||
Overexpression | Sedation | Rap Tol (Time to Sed) | Increase | |||
htl | FGF receptor | LOF mutant | Video | ACT | Decrease | King et al. (2014) |
iav | Cation channel | LOF mutant | Inebriometer | MET | Decrease | Scholz (2005) |
InR | Insulin receptor | LOF mutants | Inebriometer | MET | Decrease | Corl et al. (2005) |
Jwa | Microtubule-binding protein | Antisense RNA | Inebriometer | Rap Tol (MET) | Decrease | Li et al. (2008) |
Overexpression | Sedation recovery | Rap Tol (Sed Rec Time) | Increase | |||
KCNQ | Voltage-dependent potassium channel | LOF mutant | Sedation | Time to Sed | Decrease | Cavaliere et al. (2012) |
RNAi | Sedation | Time to Sed | Decrease | |||
Overexpression | Sedation | Rap Tol (Time to Sed) | Increase | |||
Men | Malate metabolism | LOF mutant | Inebriometer | MET | Increase | Morozova et al. (2009) |
RNAi | Inebriometer | MET | Increase | Morozova et al. (2011) | ||
Mlc-c | Myosin light chain | RNAi | Inebriometer | MET | Decrease | Morozova et al. (2011) |
moody | G protein-coupled receptor | LOF mutant | Inebriometer | MET | Increase | Bainton et al. (2005) |
mys | Integrin beta subunit | LOF mutants | eRING | Time to Sed | Decrease | Bhandari et al. (2009) |
LOF mutants | eRING | Rap Tol (Time to Sed) | Increase | |||
NmdaR1 | NMDA receptor | LOF mutant | Inebriometer | Rap Tol, Chron Tol (MET) | Decrease | Kaun et al. (2011) |
NPF | Neuropeptide F | Overexpression | Sedation | Time to Sed | Decrease | Wen et al. (2005) |
NPFR | Neuropeptide F receptor | RNAi | Sedation | Time to Sed | Increase | Wen et al. (2005) |
RNAi | CAFÉ | Alcohol Preference | Increase | Shohat-Ophir et al. (2012) | ||
Orco | Odorant receptor co-receptor | LOF mutant | Booz-o-mat | ACT | Increase | Kong et al. (2010a) |
LOF mutants | Alcohol trap | Alcohol Odor Preference | Decrease | Schneider et al. (2012) | ||
Osi9 | Unknown | GOF mutant | Inebriometer | MET | Increase | Morozova et al. (2011) |
par-1 | Serine–threonine kinase | LOF mutant | Video | ACT | Suppresses tao LOF | King et al. (2011) |
Pdk1 | PIP3-dependent serine/threonine kinase | Overexpression | Sedation | Time to Sed | Decrease | Eddison et al. (2011) |
per | CYC/CLK stability | LOF mutant | Sedation | Time to Sed | No circadian effect | van der Linde and Lyons (2011) |
LOF mutant | Sedation | Rap Tol (Time to Sed) | Decrease | |||
Pi3K21B (p60) | PI3K inhibitory subunit | Overexpression | Inebriometer | MET | Decrease | Corl et al. (2005) |
Pi3K92E (p110) | PI3K catalytic subunit | Overexpression | Sedation | Time to Sed | Decrease | Eddison et al. (2011) |
Dominant negative | Sedation | Time to Sed | Increase | |||
Pka-C1 (DCO) | PKA-catalytic subunit 1 | LOF mutants | Inebriometer | MET | Decrease | Moore et al. (1998) |
LOF mutants | Inebriometer | MET | Decrease | Rodan et al. (2002) | ||
Pka-R2 | Protein kinase A regulatory subunit | LOF mutant | Sedation | Time to Sed | Increase | Park et al. (2000) |
Pkc98E | Protein kinase C calcium independent | RNAi | Sedation | Time to Sed | Increase | Chen et al. (2008) |
RNAi | Sedation | Time to Sed | Increase | Chen et al. (2010) | ||
psq | Helix-loop-helix protein | LOF mutant | Inebriometer | MET | Decrease | Morozova et al. (2009) |
LOF mutant | Inebriometer | MET | Decrease | Morozova et al. (2011) | ||
Pten | Phosphatidylinositol 3,4,5-triphosphate phosphatase | Overexpression | Sedation | Time to Sed | Increase | Eddison et al. (2011) |
puc | Tyrosine phosphatase | LOF mutant | Booz-o-mat | ACT | Decrease | Kapfhamer et al. (2012) |
Rac1 | Small GTPase | GOF transgenic | Sedation | % Sed | Decrease | Rothenfluh et al. (2006) |
Rheb | Small GTPase | Overexpression | Sedation | Time to Sed | Decrease | Eddison et al. (2011) |
rho | Ligand-activated peptidase | LOF mutant | Sedation | Time to Sed | Decrease | Corl et al. (2009) |
Rho1 | Small GTPase | GOF transgenic | Sedation | % Sed | Decrease | Rothenfluh et al. (2006) |
RhoGAP18B | Rho Gap | LOF mutants | Video | ACT | Increase | Rothenfluh et al. (2006) |
Sedation | % Sed | Decrease | ||||
rl | ERK kinase | Overexpression | Sedation | Time to Sed | Increase | Corl et al. (2009) |
rut | Ca2+/calmodulin-sensitive adenylyl cyclase | LOF mutants | Inebriometer | MET | Decrease | Moore et al. (1998) |
LOF mutants | Booz-o-mat | ACT, % Sed | Increase | Wolf et al. (2002) | ||
LOF mutant | CAFÉ | Alcohol Preference | Decrease | Xu et al. (2012) | ||
S | Chaperone | LOF mutant | Sedation | Time to Sed | Decrease | Corl et al. (2009) |
sca | Fibrinogen | LOF mutants | Conditioned preference | Alcohol preference | Decrease | Kaun et al. (2011) |
SCAP | Unknown | GOF mutant | Inebriometer | MET | Increase | Morozova et al. (2011) |
scb | Integrin alpha subunit | LOF mutants | eRING | Time to Sed | Decrease | Bhandari et al. (2009) |
LOF mutants | eRING | Rap Tol (Time to Sed) | Increase | |||
sgl | UDP-glucose 6-dehydrogenase | LOF mutant | Inebriometer | MET | Increase | Morozova et al. (2011) |
shi | Dynamin | LOF mutants | Sedation recovery | Rap Tol (Sed Rec Time) | Decrease | Krishnan et al. (2012) |
Sip1 | Unknown | GOF mutant | Inebriometer | MET | Decrease | Morozova et al. (2011) |
Sir2 | Histone deacetylase | LOF mutant | Booz-o-mat | ACT | Decrease | Kong et al. (2010a) |
LOF mutant | Booz-o-mat | % Sed | Decrease | |||
LOF mutant | Booz-o-mat | Rap Tol (% Sed) | Decrease | |||
slo | Calcium-activated potassium channel | LOF mutants | Sedation recovery | Rap Tol (Sed Rec Time) | Decrease | Cowmeadow et al. (2005) |
Overexpression | Sedation Recovery | Rap Tol (Sed Rec Time) | Induced Rap Tol | Cowmeadow et al. (2006) | ||
LOF mutant | Seizure induction | Seizure Threshold (V) | Decrease | Ghezzi et al. (2012) | ||
spi | Epidermal growth factor receptor ligand | Overexpression | Sedation | Time to Sed | Increase | Corl et al. (2009) |
Spn27A | Serine-type endopeptidase inhibitor | LOF mutant | Booz-o-mat | ACT | Decrease | Kong et al. (2010a) |
Syn | Synapsin | LOF mutant | Inebriometer | Rap Tol (MET) | Increase | Godenschwege et al. (2004) |
Syx1A | Syntaxin | LOF mutant | Sedation recovery | Rap Tol (Sed Rec Time) | Decrease | Krishnan et al. (2012) |
Tao | Serine–threonine kinase | LOF mutant | Booz-o-mat | ACT | Decrease | King et al. (2011) |
tay | AUTS2 ortholog | LOF mutant | Sedation | Time to Sed | Increase | Schumann et al. (2011) |
RNAi | Sedation | Time to Sed | Increase | |||
Tbh | Tyramine hydroxylase | LOF mutant | Inebriometer | Rap Tol (MET) | Decrease | Scholz et al. (2000) |
LOF mutant | Inebriometer | Rap Tol (MET) | Decrease | Berger et al. (2004) | ||
LOF mutant | Inebriometer | Rap Tol (MET) | Decrease | Scholz et al. (2005) | ||
LOF mutant | Sedation | Rap Tol (Time to Sed) | Decrease | Awofala et al. (2011) | ||
LOF mutants | Alcohol trap | Odor Preference | Decrease | Schneider et al. (2012) | ||
tim | CYC/CLK stability | LOF mutant | Sedation | Rap Tol (Time to Sed) | Decrease | Pohl et al. (2013) |
tra | Female-specific mRNA splicing protein | Overexpression (♂) | Sedation | Time to Sed | Decrease | Devineni and Heberlein (2012) |
RNAi (♀) | Sedation | Time to Sed | Increase | |||
Tre1 | G protein-coupled receptor | GOF mutant | Inebriometer | MET | Increase | Morozova et al. (2011) |
unc-13 | Calmodulin binding; diacylglycerol binding | LOF mutant | CAFÉ | Alcohol Preference | Increase | Das et al. (2013) |
tank | EI24/PIG8 ortholog | LOF mutant, RNAi | Booz-o-mat | Time to Sed | Increase | Devineni et al. (2013) |
w | ABC transporter | LOF mutant | eRING | Time to Sed | Decrease | Chan et al. (2014) |
RNAi | eRING | Time to Sed | Decrease | Chan et al. (2014) | ||
LOF mutant | Fly Bar | Time to LORR | Increase | van der Linde et al. (2014) |
Columns are the gene name abbreviations, a brief functional description of the gene product, the type of genetic manipulation that was used (LOF, loss of function; RNAi, RNA interference, or overexpression), the name of the assay used to assess alcohol-related behavior, the behavioral end point that was measured in the assay (ACT, alcohol-stimulated locomotor activity or locomotor activity in the presence of alcohol; % Sed, % of flies sedated after a defined exposure to alcohol; MET, mean elution time; Rap Tol and Chron Tol, rapid tolerance and chronic tolerance, respectively, to the behavioral measure indicated in parentheses; Time to Sed, duration of alcohol exposure required to sedate flies to a defined level; Sed Rec Time, time required for flies to recover from sedation; Alcohol Preference, alcohol drinking preference; Time to LORR, alcohol exposure time required for flies to lose a defined amount of their ability to right themselves; Seizure Threshold (V), voltage of electric shock required to produce seizures in a defined fraction of subjects; Alcohol Odor Preference, fraction of flies captured in a trap with alcohol odor vapor), the effect of the genetic manipulation on the behavioral measure, and the citations for the relevant publications.