Table 2.
Genes that Influence Alcohol-Related Behavior in Worms
| Gene | Function | Genetic manipulation | Behavioral assay | Measure | Effect | Citation |
|---|---|---|---|---|---|---|
| aex-3 | RAB3 GTP exchange factor | LOF mutant | Crawling (400 mM) | Crawling speed at 20 minutes | Resistant | Kapfhamer et al. (2008) |
| alh-13 | Aldehyde dehydrogenase | RNAi | Crawling (400 mM) | Crawling speed at 10 minutes | Sensitive | Alaimo et al. (2012) |
| alh-6 | Aldehyde dehydrogenase | RNAi | Crawling (400 mM) | Crawling speed at 10 minutes | Sensitive | Alaimo et al. (2012) |
| bbs-1 | BBS1 | LOF mutant | Crawling (400 mM) | Crawling speed at 10 and 30 minutes; initial sensitivity and AFT | Increased IS; Enhanced AFT | Bettinger et al. (2012) |
| cat-1 | Vesicular monoamine transporter | LOF mutant | State-dependent learning | SDL | Fails to develop SDL | Bettinger and McIntire (2004) |
| cat-2 | Tyrosine hydroxylase | LOF mutant | State-dependent learning; Alcohol preference | SDL; Alcohol preference | Fails to develop SDL Does not develop Alcohol preference | Bettinger and McIntire (2004), Lee et al. (2009) |
| cha-1 | Cholineacetyltransferase | LOF mutant | Hypercontraction | Hypercontraction and Recovery | Resistant | Hawkins et al. (2015) |
| ctbp-1 | Transcriptional co-repressor | LOF mutant | Crawling (400 mM) | Crawling speed at 10 and 30 minutes; initial sensitivity and AFT | Increased IS; Decreased AFT | Bettinger et al. (2012) |
| dgk-1 | Diacylglycerol kinase | LOF mutant | Crawling (500 mM) Crawling (400 mM) |
Crawling speed at 20 minutes; Crawling speed; initial sensitivity and AFT | Resistant; Decrease in IS | Bettinger et al. (2012), Davies et al. (2003) |
| dpff-1 | Component of SWI/SNF chromatin remodeling complex | RNAi | Crawling (400 mM) | Crawling speed at 10 and 30 minutes; initial sensitivity and AFT | Decreased IS | Mathies et al. (2015) |
| dop-4 | Dopamine receptor (D1-like) | LOF mutant | Alcohol disinhibition of crawling gait in liquid | Body posture in liquid (500 mM) | Resistant to Alcohol disinhibition of crawling gait in liquid | Topper et al. (2014) |
| eat-6 | Alpha subunit Na+/K+-ATPase | LOF mutant | Hypercontraction | Hypercontraction and recovery | No recovery from hypercontraction | Hawkins et al. (2015) |
| egl-3 | Proprotein convertase | LOF mutant | Alcohol withdrawal-induced “unaccompanied” omega turns (350 mM) | Number of omega turns without a preceding reversal at 5 and 40 minutes | No increase in “unaccompanied” omega turns | Mitchell et al. (2010) |
| exc-4 | CLIC; numerous proposed | LOF mutant | Crawling (400 mM), 10, 20, 30, 40, 50 minutes | Crawling speed at 10, 20, 30, 40, 50 minutes | Decrease in IS at 10 minutes; trend toward decrease in AFT | Bhandari et al. (2012) |
| exl-1 | CLIC; numerous proposed | LOF mutant | Crawling (400 mM), 10, 20, 30, 40, 50 minutes | Crawling speed at 10, 20, 30, 40, 50 minutes | Enhanced AFT | Bhandari et al. (2012) |
| fat-1 | Omega-3 fatty acid acyl desaturase | LOF mutant | Crawling (400 mM) | Crawling speed at 10 and 30 minutes; initial sensitivity and AFT | Increased IS; No AFT | Raabe et al. (2014) |
| fat-3 | Delta-6 fatty acid desaturase | LOF mutant | Crawling (400 mM) | Crawling speed at 10 and 30 minutes; initial sensitivity and AFT | No AFT | Raabe et al. (2014) |
| fat-4 | Delta-5 fatty acid desaturase | LOF mutant | Crawling (400 mM) | Crawling speed at 10 and 30 minutes; initial sensitivity and AFT | No AFT | Raabe et al. (2014) |
| let-526 | Component of SWI/SNF chromatin remodeling complex | RNAi | Crawling (400 mM) | Crawling speed at 10 and 30 minutes; initial sensitivity and AFT | Decreased IS | Mathies et al. (2015) |
| lips-7 | Triacylglycerol lipase | LOF mutant | Crawling (400 mM) | Crawling speed at 10 and 30 minutes; initial sensitivity and AFT | Decreased IS; Enhanced AFT | Bettinger et al. (2012) |
| nca-1 | NALCN-related leak channel | LOF mutant | Swimming (400 mM) | Frequency of body bends at 10 minutes | Sensitive | Speca et al. (2010) |
| nca-2 | NALCN-related leak channel | LOF mutant | Swimming (400 mM) | Frequency of body bends at 10 minutes | Sensitive | Speca et al. (2010) |
| nhr-49 | Nuclear hormone receptor | LOF mutant | Crawling (400 mM) | Crawling speed at 10 and 30 minutes; initial sensitivity and AFT | No AFT | Bettinger et al. (2012) |
| npr-1 | Neuropeptide Y-like GPCR | LOF mutants | Crawling (500 mM) Crawling (400 mM) |
Crawling speed at 10, 30, 50 minutes; initial sensitivity and AFT Crawling speed at 10 and 30 minutes; initial sensitivity and AFT |
Decreased IS; Enhanced AFT; Decreased IS; Enhanced AFT | Bettinger et al. (2012), Davies et al. (2004) |
| osm-9 | TRPV channel | LOF mutant | Crawling (500 mM) | Crawling speed at 10, 30, 50 minutes; initial sensitivity and AFT | Partial suppression of npr-1 enhanced AFT | Davies et al. (2004) |
| pag-3 | Zinc-finger transcription factor | LOF mutant | Crawling (400 mM) | Crawling speed at 10 and 30 minutes; initial sensitivity and AFT | No AFT | Bettinger et al. (2012) |
| pbrm-1 | Component of SWI/SNF chromatin remodeling complex | LOF mutant | Crawling (400 mM) | Crawling speed at 10 and 30 minutes; initial sensitivity and AFT | Decreased AFT | Mathies et al. (2015) |
| phf-10 | Component of SWI/SNF chromatin remodeling complex | RNAi | Crawling (400 mM) | Crawling speed at 10 and 30 minutes; initial sensitivity and AFT | No AFT | Mathies et al. (2015) |
| rab-3 | Small molecular weight GTP-binding protein | LOF mutant | Dispersal assay (200 and 400 mM); Crawling (400 mM) | Movement toward food; Crawling speed at 20 minutes | Fast dispersal; Resistant | Kapfhamer et al. (2008) |
| sbp-1 | Transcription factor | LOF mutant | Crawling (400 mM) | Crawling speed at 10 and 30 minutes; initial sensitivity and AFT | Decreased IS; No AFT | Bettinger et al. (2012) |
| seb-3 | CRF receptor-like GPCR | LOF mutant GOF mutant |
Crawling (500 mM) Withdrawal induced tremor (400 mM) |
Crawling speed at 10, 30, 50 minutes, AFT; Number of animals with tremor after withdrawal from 4-hour exposure | LOF: Decreased AFT, GOF: Increased AFT; LOF: Resistant to tremor | Jee et al. (2013) |
| sir-2.1 | Transcription factor | LOF mutant | Crawling (400 mM) | Crawling speed at 10 and 30 minutes; initial sensitivity and AFT | Decreased IS; Enhanced AFT | Bettinger et al. (2012) |
| slo-1 | BK voltage and calcium-sensitive large conductance K+ channel | LOF mutants | Crawling (500 mM) Egg laying (500 mM) Crawling (400 mM) |
Crawling speed at 20 minutes; Number of eggs laid on Alcohol; Crawling speed at 10 and 30 minutes; initial sensitivity and AFT | Resistant; Resistant; Decreased IS; Decreased AFT | Bettinger et al. (2012), Davies et al. (2003), Dillon et al. (2013) |
| sodh-1 | Alcohol dehydrogenase | LOF mutants | Crawling (200 mM); Crawling (400 mM) | Crawling speed at 10 and 50 minutes; Crawling speed at 10 and 50 minutes; initial sensitivity and AFT | Resistant; Resistant | Alaimo et al. (2012) |
| swsn-1 | Component of SWI/SNF chromatin remodeling complex | LOF mutant | Crawling (400 mM) | Crawling speed at 10 and 30 minutes; initial sensitivity and AFT | No AFT | Mathies et al. (2015) |
| swsn-2.1 | Component of SWI/SNF chromatin remodeling complex | LOF mutant | Crawling (400 mM) | Crawling speed at 10 and 30 minutes; initial sensitivity and AFT | No AFT | Mathies et al. (2015) |
| swsn-2.2 | Component of SWI/SNF chromatin remodeling complex | LOF mutant | Crawling (400 mM) | Crawling speed at 10 and 30 minutes; initial sensitivity and AFT | Decreased IS; No AFT | Mathies et al. (2015) |
| swsn-3 | Component of SWI/SNF chromatin remodeling complex | LOF mutant | Crawling (400 mM) | Crawling speed at 10 and 30 minutes; initial sensitivity and AFT | Increased IS; No AFT | Mathies et al. (2015) |
| swsn-4 | Component of SWI/SNF chromatin remodeling complex | LOF mutant | Crawling (400 mM) | Crawling speed at 10 and 30 minutes; initial sensitivity and AFT | No AFT | Mathies et al. (2015) |
| swsn-6 | Component of SWI/SNF chromatin remodeling complex | RNAi | Crawling (400 mM) | Crawling speed at 10 and 30 minutes; initial sensitivity and AFT | Decreased IS; No AFT | Mathies et al. (2015) |
| swsn-7 | Component of SWI/SNF chromatin remodeling complex | LOF mutant | Crawling (400 mM) | Crawling speed at 10 and 30 minutes; initial sensitivity and AFT | Decreased IS | Mathies et al. (2015) |
| swsn-9 | Component of SWI/SNF chromatin remodeling complex | LOF mutant | Crawling (400 mM) | Crawling speed at 10 and 30 minutes; Initial sensitivity and AFT | No AFT | Mathies et al. (2015) |
| tph-1 | Tryptophan hydroxylase | LOF mutant | Alcohol preference | Alcohol preference | Decrease in preference | Lee et al. (2009) |
| unc-17 | Vesicular acetylcholine transporter | LOF mutant | Hypercontraction | Hypercontraction and Recovery | Resistant to Hypercontraction | Hawkins et al. (2015) |
| unc-18 | SM protein | LOF mutant | Swimming (400 mM) | Number of thrashes at 10 minutes | Resistant | Graham et al. (2009) |
| unc-25 | Glutamic acid decarboxylase | LOF mutant | Hypercontraction | Hypercontraction and Recovery | Resistant to Hypercontraction | Hawkins et al. (2015) |
| unc-47 | GABA vesicular transporter | LOF mutant | Hypercontraction | Hypercontraction and Recovery | Resistant to Hypercontraction | Hawkins et al. (2015) |
| unc-63 | Nicotinic acetylcholine receptor | LOF mutant | Hypercontraction | Hypercontraction and Recovery | Resistant to Hypercontraction | Hawkins et al. (2015) |
| unc-79 | Interacts with voltage insensitive cation leak channels | LOF mutant | Immobility over a dose curve; Swimming (400 mM) | EC50 (immobility) at 5 minutes Frequency of body bends at 10 minutes |
Resistant; Sensitive | Morgan and Sedensky (1995), Speca et al. (2010) |
| unc-80 | Interacts with voltage insensitive cation leak channels | LOF mutant | Swimming (400 mM) | Frequency of body bends at 10 minutes | Sensitive | Speca et al. (2010) |
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 mutation; GOF, gain of function mutation; RNAi, RNA interference), the name of the assay used to assess alcohol-related behavior, the behavioral end point that was measured in the assay (Crawling speed, locomotion speed on an agar surface; Swimming, number of body bends or thrashes in a liquid medium; SDL, state-dependent learning; Alcohol preference; Hypercontraction; Alcohol disinhibition of crawling gait in a liquid assay; Alcohol withdrawal-induced “unaccompanied” omega turns, omega turns observed without accompanying reversal; Dispersal assay; Alcohol withdrawal-induced tremor; Egg-laying; Immobility in liquid), the effect of the genetic manipulation on the behavioral measure, and the citations for the relevant publications.