Dopamine (DA) is a catecholamine neurotransmitter that regulates many aspects of motivated behavior in animals. Extracellular DA is highly regulated by the presynaptic high-affinity dopamine transporter (DAT), and drug- or genetically induced deficiencies in DAT function result in loss of DA reuptake. Mice in which DAT expression has been ablated have been previously proposed to be a relevant model of attention deficit hyperactivity disorder and have led to mechanistic insights regarding psychostimulant drug actions. However, very little previous work has emphasized the biobehavioral development of DAT-deficient mice. We therefore examined motoric, emotional and cognitive phenotypes in preadolescent (P22–26) DAT mutant mice. Consistent with previous reports in adult DAT^–/– mice, we observed a hyperlocomotive phenotype in preadolescent mice across multiple assays. Somewhat surprisingly, spatial working memory in a Y-maze appeared intact, suggesting that cognitive phenotypes may emerge relatively late in development following hyperdopaminergia. Anxiety levels appeared to be reduced in DAT^–/– mice, as defined by elevated plus maze and light-dark preference assays. No significant differences were observed between wild-type and heterozygous mice, suggesting a minimal impact of DAT haploinsufficiency on neurobehavioral status. Taken together, these data for the first time establish behavioral phenotypes of DAT mutant mice during development and suggest complex developmental stage-dependent effects of DA signaling on cognitive and emotional behaviors.

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The global expansion of biomanufacturing is currently limited by the availability of sugar-based microbial feedstocks, which require farmland for cultivation and therefore cannot support large increases in production without impacting the human food supply. One-carbon feedstocks, such as methanol, present an enticing alternative to sugar because they can be produced independently of arable farmland from organic waste, atmospheric carbon dioxide, and hydrocarbons such as biomethane, natural gas, and coal. The development of efficient industrial microorganisms that can convert one-carbon feedstocks into valuable products is an ongoing challenge. This review discusses progress in the field of synthetic methylotrophy with a focus on how it pertains to the important industrial yeast, Saccharomyces cerevisiae. Recent insights generated from engineering synthetic methylotrophic xylulose- and ribulose-monophosphate cycles, reductive glycine pathways, and adaptive laboratory evolution studies are critically assessed to generate novel strategies for the future engineering of methylotrophy in S. cerevisiae.