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 nervous system. Thus, their local expression in the CNS of transgenic mice could be used to perturb the function of the corresponding antigen. As a first application of this approach, we have generated transgenic mice 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 developmentally regulated manner and are effective in competing with the endogenous substance P, as demonstrated by a marked inhibition of neurogenic inflammation and by motor deficits. This phenotypic knockout approach may provide a complementary alternative to gene knockout by homologous recombination.
Piccioli
P
P
International School for Advanced Studies (SISSA), International Center for Genetic Engineering and Biotechnology, Trieste, Italy.
Di Luzio
A
A
Amann
R
R
Schuligoi
R
R
Surani
M A
MA
Donnerer
J
J
Cattaneo
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics / Q000276:immunology; D001921:Brain / Q000378:metabolism*; D004924:Escape Reaction / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D051379:Mice; D008822:Mice, Transgenic; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009479:Neuropeptides; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D013373:Substance P / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000502:physiology; D014158:Transcription, Genetic
D000911:Antibodies, Monoclonal; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D011506:Proteins; D011993:Recombinant Fusion Proteins; C512697:Vgf protein, mouse; C062040:Vgf protein, rat; D013373:Substance P