Not only has forward mutagenesis been an invaluable approach in C. elegans and Drosophila for the study of the nervous system, more recent forward mutagenesis efforts in mice have isolated numerous mutants that influence a variety of behavioral phenotypes [19]–[22]. We previously performed a mouse forward mutagenesis screen using a sensitized genetic background based on a heterozygous null mutation in the dopamine transporter (DAT) to enrich for dominant mutations that enhance dopaminergic neurotransmission [23]. This screen successfully identified five loci that influence locomotor behavior in a quantitative manner, two of which were dependent on the sensitized background and three of which acted independently of the sensitized background. Here we report that the dominant behavioral phenotype of one of the independent loci, Lightweight (Lwt), results from a nonsense mutation in the mouse homolog of the C. elegans unc-79 gene. Lightweight heterozygotes are mildly hyperactive and have altered response to ethanol and inhaled anesthetics, consistent with a conserved function of the mammalian unc-79 gene product.
