title: Neuroligin-deficient mutants of C. elegans have sensory processing deficits and are hypersensitive to oxidative stress and mercury toxicity.
abstract: Neuroligins are postsynaptic cell adhesion proteins that bind specifically to presynaptic membrane proteins called neurexins. Mutations in human neuroligin genes are associated with autism spectrum disorders in some families. The nematode Caenorhabditis elegans has a single neuroligin gene (nlg-1), and approximately a sixth of C. elegans neurons, including some sensory neurons, interneurons and a subset of cholinergic motor neurons, express a neuroligin transcriptional reporter. Neuroligin-deficient mutants of C. elegans are viable, and they do not appear deficient in any major motor functions. However, neuroligin mutants are defective in a subset of sensory behaviors and sensory processing, and are hypersensitive to oxidative stress and mercury compounds; the behavioral deficits are strikingly similar to traits frequently associated with autism spectrum disorders. Our results suggest a possible link between genetic defects in synapse formation or function, and sensitivity to environmental factors in the development of autism spectrum disorders.
authors.affiliation: Genetic Models of Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
authors.forename: Jerrod W
authors.initials: JW
authors.lastname: Hunter
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Mullen
authors.forename: John R
authors.initials: JR
authors.lastname: McManus
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Heatherly
authors.forename: Angie
authors.initials: A
authors.lastname: Duke
authors.forename: James B
authors.initials: JB
authors.lastname: Rand
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D003463:Cues; D017930:Genes, Reporter; D006801:Humans; D008628:Mercury / Q000633:toxicity*; D032342:Muscle Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D021381:Protein Transport / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012677:Sensation / Q000187:drug effects*; D017386:Sequence Homology, Amino Acid; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D013696:Temperature
chemical_list: D015415:Biomarkers; D015816:Cell Adhesion Molecules, Neuronal; D011993:Recombinant Fusion Proteins; C093438:neuroligin 1; D008628:Mercury