Selective ablation of olfactory receptor neurons without functional impairment of vomeronasal receptor neurons in OMP-ntr transgenic mice.
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.
Ma
Dan
D
Sub-Department of Animal Behaviour, University of Cambridge, High Street, Madingley, CB3 8AA, UK.
Allen
Nicholas D
ND
Van Bergen
Yfke C H
YC
Jones
Camilla M E
CM
Baum
Michael J
MJ
Keverne
E Barry
EB
Brennan
Peter A
PA
D000818:Animals; D001388:Aziridines / Q000378:metabolism / Q000494:pharmacology; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000139:chemically induced / Q000201:enzymology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009498:Neurotoxins / Q000378:metabolism / Q000494:pharmacology; D009601:Nitroreductases / Q000235:genetics / Q000378:metabolism*; D051842:Olfactory Marker Protein; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D011247:Pregnancy / Q000187:drug effects / Q000502:physiology; D012724:Sex Attractants / Q000494:pharmacology; D019147:Vomeronasal Organ / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*
D001388:Aziridines; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D051842:Olfactory Marker Protein; C497598:Omp protein, mouse; D012724:Sex Attractants; C100099:tretazicar; D009601:Nitroreductases