Intracerebroventricular infusion of CHO5, a rat monoclonal antibody directed against mouse low-affinity nerve growth factor receptor (p75NTR), specifically labels basal forebrain cholinergic neurons in mouse brain

The finding that basal forebrain cholinergic cells are specifically endowed with the low-affinity nerve growth factor receptor p75NTR has been employe d to develop a cholinergic immunotoxin in rats by covalently linking the mo noclonal antibody 192IgG against the rat p75(NTR) With the cytotoxic protei n saporin (192IgG-saporin). Following intracebroventricular application of 192IgC-saporin, the antibody conjugate is taken up into cholinergic cells v ia the p75(NTR), retrogradely transported to the cell body, where saporin e xerts cytotoxic action. The lack of an appropriate antibody directed agains t mouse p75(NTR) has been hampered the development of a mouse-specific chol inergic immunotoxin, which should be a useful tool to study effects of cort ical cholinergic deficits on processing of amyloid precursor protein in tra nsgenic mice with Alzheimer pathology. To develop an appropriate mouse-spec ific immunotoxin, a variety of antibodies directed against mouse p75(NTR) w ere tested. Using double labeling immunocytochemistry, the rat monoclonal a ntibody CHO5 against mouse p75(NTR) was found to label mouse basal forebrai n neurons, which also demonstrated immunoreactivity for choline acetyltrans ferase and the high-affinity nerve growth factor receptor, TrkA. Intracereb roventricular infusion of CHO5 in mice resulted in an accumulation of the a ntibody in cholinergic cells within the basal forebrain, suggesting that CH O5 is a suitable candidate to develop a mouse-specific cholinergic immunoto xin.