Quantitative trait loci for sensitivity to ethanol intoxication in a C57BL/6J × 129S1/SvImJ inbred mouse cross

Individual variation in sensitivity to acute ethanol (EtOH) challenge is associated with alcohol drinking and is a predictor of alcohol abuse. Previous studies have shown that the C57BL/6J (B6) and 129S1/SvImJ (S1) inbred mouse strains differ in responses on certain measures of acute EtOH intoxication. To gain insight into genetic factors contributing to these differences, we performed quantitative trait locus (QTL) analysis of measures of EtOH-induced ataxia (accelerating rotarod), hypothermia, and loss of righting reflex (LORR) duration in a B6 × S1 F2 population. We confirmed that S1 showed greater EtOH-induced hypothermia (specifically at a high dose) and longer LORR compared to B6. QTL analysis revealed several additive and interacting loci for various phenotypes, as well as examples of genotype interactions with sex. QTLs for different EtOH phenotypes were largely non-overlapping, suggesting separable genetic influences on these behaviors. The most compelling main-effect QTLs were for hypothermia on chromosome 16 and for LORR on chromosomes 4 and 6. Several QTLs overlapped with loci repeatedly linked to EtOH drinking in previous mouse studies. The architecture of the traits we examined was complex but clearly amenable to dissection in future studies. Using integrative genomics strategies, plausible functional and positional candidates may be found. Uncovering candidate genes associated with variation in these phenotypes in this population could ultimately shed light on genetic factors underlying sensitivity to EtOH intoxication and risk for alcoholism in humans

The cys-loop ligand-gated ion channel gene superfamily of the parasitoid wasp, Nasonia vitripennis.

Members of the cys-loop ligand-gated ion channel (cysLGIC) superfamily mediate chemical neurotransmission and are studied extensively as potential targets of drugs used to treat neurological disorders, such as Alzheimer's disease. Insect cys-loop LGICs also have central roles in the nervous system and are targets of highly successful insecticides. Here, we describe the cysLGIC superfamily of the parasitoid wasp, Nasonia vitripennis, which is emerging as a highly useful model organism and is deployed as a biological control of insect pests. The wasp superfamily consists of 26 genes, which is the largest insect cysLGIC superfamily characterized, whereas Drosophila melanogaster, Apis mellifera and Tribolium castaneum have 23, 21 and 24, respectively. As with Apis, Drosophila and Tribolium, Nasonia possesses ion channels predicted to be gated by acetylcholine, gamma-amino butyric acid, glutamate and histamine, as well as orthologues of the Drosophila pH-sensitive chloride channel (pHCl), CG8916 and CG12344. Similar to other insects, wasp cysLGIC diversity is broadened by alternative splicing and RNA A-to-I editing, which may also serve to generate species-specific receptor isoforms. These findings on N. vitripennis enhance our understanding of cysLGIC functional genomics and provide a useful basis for the study of their function in the wasp model, as well as for the development of improved insecticides that spare a major beneficial insect species