Title: | Selective ablation of olfactory receptor neurons without functional impairment of vomeronasal receptor neurons in OMP-ntr transgenic mice |
Author(s): | Ma D; Allen ND; Van Bergen YC; Jones CM; Baum MJ; Keverne EB; Brennan PA; |
Address: | "Sub-Department of Animal Behaviour, University of Cambridge, High Street, Madingley, CB3 8AA, UK" |
DOI: | 10.1046/j.1460-9568.2002.02303.x |
ISSN/ISBN: | 0953-816X (Print) 0953-816X (Linking) |
Abstract: | "This study used transgenic mice, in which expression of a bacterial nitroreductase (ntr) gene was linked to the expression of olfactory marker protein (OMP). The nitroreductase enzyme is thus expressed in mature chemosensory neurons of these OMP-ntr transgenic mice, and converts the pro-drug CB1954 to a cytotoxic form, specifically killing these neurons. Systemic injections of the pro-drug led to the ablation of receptor neurons in both the main olfactory and vomeronasal epithelia. Due to the anatomical separation of the epithelia, however, when the pro-drug was administered by intranasal infusion only the receptors of the main olfactory epithelium were destroyed. This procedure resulted in a profound deficit in olfactory investigation and discrimination in a habituation-dishabituation test, whereas the pregnancy blocking effect of male pheromones, which is mediated via the vomeronasal system was unaffected. OMP-ntr mice receiving intranasal infusion of pro-drug had not recovered any significant main olfactory function at 24 days following treatment. This novel technique could potentially be applied to selectively ablate olfactory receptor neurons expressing a particular olfactory receptor by linking its expression to that of the nitroreductase enzyme" |
Keywords: | "Animals Aziridines/metabolism/pharmacology Cell Count Cell Death/drug effects/*physiology Epithelial Cells/cytology/drug effects/enzymology Female Immunohistochemistry Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Transgenic Nerve Degeneration/ch;" |
Notes: | "MedlineMa, Dan Allen, Nicholas D Van Bergen, Yfke C H Jones, Camilla M E Baum, Michael J Keverne, E Barry Brennan, Peter A eng MH59200/MH/NIMH NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. France 2002/12/21 Eur J Neurosci. 2002 Dec; 16(12):2317-23. doi: 10.1046/j.1460-9568.2002.02303.x" |