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Publisher Summary Caenorhabditis elegans are widely used as powerful tools for the analysis of mutants and genes. From the perspective of a mammalian neurobiologist, there are two basic strategies that may profitably be employed using C. elegans . Firstly, the basic information derived from C. elegans biology and molecular genetics is applied to mammalian systems; that is, genes first characterized in C. elegans are used to identify mammalian homologues. The other powerful use of C. elegans is to start with known mammalian biology and genes and then identify the C. elegans homologues of these genes. The availability of a large collection of C. elegans mutants has permitted careful in vivo analysis of cholinergic regulation and the behavioral consequences of cholinergic hypofunction. Animals completely lacking the vesicular acetylcholine transporter (VAChT) protein cannot grow or survive after hatching. Animals with milder mutations in the unc-17 gene are small, slow-growing, and display a number of neurornuscular deficits. They are also quite strongly resistant to inhibitors of acetylcholinesterase. All of these phenotypes are shared by cha-1 mutants that argue that vesicular transport is necessary for cholinergic function. Three amine neurotransmitters have been identified thus far in C. elegans : Dopamine (DA), formaldehyde-induced fluorescence (FIF), and serotonin (5HT). The C. elegans Genome Sequencing Project has identified a genomic sequence that appeared to encode part of a vesicular monoamine transporter (VMAT)-like protein. The C. elegans VMAT homologue appears to be encoded by the previously identified cat-2 gene. Using these transporter genes and mutants, together with standard C. elegans tools, it can be now possible to analyze the differentiation of particular neuronal cell types and also the contribution of particular protein domains to cellular and overall behavioral function. |
