The purpose of this project is to develop improved methods to study the motorneuron with a primary long-term goal of furthering our understanding of the susceptibility of this cell to amyotrophic lateral sclerosis and the spinal muscular atrophies. The project's central focus will be an investigation of antigenic determinants on motorneurons using monoclonal antibodies (MAB's). MAB's binding motorneuron antigens will be raised using two strategies: (1) immunization of mice with anterior horn cell membrane preparations and neurons from fetal spinal cord, an approach which has proven feasible in our preliminary studies, and (2) generation of monoclonal antibodies which recognize the poliovirus receptor, a surface marker for this cell. This will be accomplished by first raising monoclonal antibodies which neutralize the virus and then by generating a second set of antibodies against those which neutralize. Such """"""""antiidiotype"""""""" antibodies have been shown in an analogous Reovirus system in this laboratory to recapitulate the binding properties of the original virus, binding to the viral receptor. Molecular properties of antigens recognized by either category of MAB's will be determined using standard techniques. MAB's directed against anterior horn cells will be directly useful as probes of normal and abnormal motorneurons both in vivo and in vitro. They may also be of considerable indirect use by facilitating the isolation and range of immunological, biochemical and electrophysiological studies of these cells. They will also enhance studies of motorneuron development, synaptogenesis and trophic influences from other cells in the nervous system.
