ArticlePLoS genetics2013
A genome-wide RNAi screen in Caenorhabditis elegans identifies the nicotinic acetylcholine receptor subunit ACR-7 as an antipsychotic drug target.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- Drug screens using the nematode Caenorhabditis elegans.Genetics · 2025Review
- Behavioral and genetic analysis of the effects of the psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI) in C. elegans.PloS one · 2025Article
- RNA polymerase II CTD S2P is dispensable for embryogenesis but mediates exit from developmental diapause inScience advances · 2020Article
- Article
- Pharming for Genes in Neurotransmission: Combining Chemical and Genetic Approaches in Caenorhabditis elegans.ACS chemical neuroscience · 2018Review
- Exploring Potential Germline-Associated Roles of the TRIM-NHL Protein NHL-2 Through RNAi Screening.G3 (Bethesda, Md.) · 2017Article
- Clozapine Modulates Glucosylceramide, Clears Aggregated Proteins, and Enhances ATG8/LC3 in Caenorhabditis elegans.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Article
- Forward Genetic Screen inFrontiers in molecular neuroscience · 2016Article
- Challenges in understanding psychiatric disorders and developing therapeutics: a role for zebrafish.Disease models & mechanisms · 2015Review
- Drug-dependent behaviors and nicotinic acetylcholine receptor expressions in Caenorhabditis elegans following chronic nicotine exposure.Neurotoxicology · 2015Article
- C. elegans in high-throughput drug discovery.Advanced drug delivery reviews · 2014Review
- Methods for studying the mechanisms of action of antipsychotic drugs in Caenorhabditis elegans.Journal of visualized experiments : JoVE · 2014Article
- Drug elucidation: invertebrate genetics sheds new light on the molecular targets of CNS drugs.Frontiers in pharmacology · 2014Review
- Exploring the genetic underpinnings of brain and behavioral disorders.Journal of neurogeneticsArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
We report a genome-wide RNA interference (RNAi) screen for Suppressors of Clozapine-induced Larval Arrest (scla genes) in Caenorhabditis elegans, the first genetic suppressor screen for antipsychotic drug (APD) targets in an animal. The screen identifies 40 suppressors, including the α-like nicotinic acetylcholine receptor (nAChR) homolog acr-7. We validate the requirement for acr-7 by showing that acr-7 knockout suppresses clozapine-induced larval arrest and that expression of a full-length translational GFP fusion construct rescues this phenotype. nAChR agonists phenocopy the developmental effects of clozapine, while nAChR antagonists partially block these effects. ACR-7 is strongly expressed in the pharynx, and clozapine inhibits pharyngeal pumping. acr-7 knockout and nAChR antagonists suppress clozapine-induced inhibition of pharyngeal pumping. These findings suggest that clozapine activates ACR-7 channels in pharyngeal muscle, leading to tetanus of pharyngeal muscle with consequent larval arrest. No APDs are known to activate nAChRs, but a number of studies indicate that α7-nAChR agonists may prove effective for the treatment of psychosis. α-like nAChR signaling is a mechanism through which clozapine may produce its therapeutic and/or toxic effects in humans, a hypothesis that could be tested following identification of the mammalian ortholog of C. elegans acr-7.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.