NEUROANTIBODIES - ECTOPIC EXPRESSION OF A RECOMBINANT ANTI-SUBSTANCE-P ANTIBODY IN THE CENTRAL-NERVOUS-SYSTEM OF TRANSGENIC MICE

Recombinant antibodies are efficiently secreted by cells of the nervou s system. Thus, their local expression in the CNS of transgenic mice c ould be used to perturb the function of the corresponding antigen. As a first application of this approach, we have generated transgenic mic e that express antibodies against the neuropeptide substance P, under the transcriptional control of the promoter of the neuronal gene vgf. The transgenic antibodies are expressed in a tissue-specific and devel opmentally regulated manner and are effective in competing with the en dogenous substance P, as demonstrated by a marked inhibition of neurog enic inflammation and by motor deficits. This phenotypic knockout appr oach may provide a complementary alternative to gene knockout by homol ogous recombination.