The development of the incredibly complex cytoarchitecture of the nervous system is dependent upon the specificity of neuron:neuron and neuron:glial cell intereactions. One molecule that appears to play a pivotal role in cell:cell interactions is the homophilic adhesion molecule, N-CAM. There are a number of forms of N-CAM, but the N-CAM 180 is the only isoform that is expressed exclusively in the nervous system. Immunocytochemical studies show that this form is localized at developing synapses. These observations suggest that the sequences encoded by exon 18 of the N-CAM gene may play a unique role in synapse formation. This Small Grant for Exploratory Research will allow the PI to examine the role of N-CAM 180 in synapse formation. The neural specific exon of the N-CAM gene will be deleted in murine embryonic stem cells via homologous recombination. Transgenic mice homozygous for the deleted gene will be made and studied for overt behavioral abnormalities and defects in synapse formation. These studies represent a newly emerging approach to directly study the function of specific molecules in neural development in mammals using gene targeting technology.
