Genes encode the information needed to construct and operate the nervous system. In humans, mutations which distort this information can result in hereditary neurological and neuromuscular diseases. Behavioral mutations also occur in much simpler organisms, such as nematodes, where they can be studied genetically and at the molecular level in great detail. The C. elegans deg-1 gene can mutate to produce a dominantly transmitted phenotype of neuronal degeneration . Such mutants lose the ability to respond to mechanosensory stimulation of the tail due to late-onset degeneration of a pair of interneurons mediating tail touch response. Both the dominant mutant and wild-type deg-1 genes have recently been cloned. Injection of the mutant DNA into oocytes results in transmission of the degeneration phenotype to transformed animals. The goal of the experiments proposed here is to determine what the product of the deg-1 gene is, when and in what cells it is expressed, how spatial and temporal expression is regulated, and whether the dominant mutation resides within regulatory or coding elements of the gene. The answers to these questions may be relevant to dominantly-inherited, late-onset human neurodegenerative diseases, such as Huntington's Disease and Familial Alzheimer's Disease. The complete amino acid sequence of the deg-1 gene product will be obtained through sequence analysis of genomic and cDNA sequences. Partial sequence data available now suggest that deg-1 DNA modified in vitro in transformed animals. Novel extragenic mutations suppressing the dominant mutations will be sought in transformants carrying multiple copies of the mutant gene. Such suppressors will identify other genes which play a role in the degeneration process.
|Shreffler, W; Magardino, T; Shekdar, K et al. (1995) The unc-8 and sup-40 genes regulate ion channel function in Caenorhabditis elegans motorneurons. Genetics 139:1261-72