title: Olfactory receptor and neural pathway responsible for highly selective sensing of musk odors.
abstract: Musk odorants are used widely in cosmetic industries because of their fascinating animalic scent. However, how this aroma is perceived in the mammalian olfactory system remains a great mystery. Here, we show that muscone, one musk odor secreted by various animals from stink glands, activates a few glomeruli clustered in a neuroanatomically unique anteromedial olfactory bulb. The muscone-responsive glomeruli are highly specific to macrocyclic ketones; interestingly, other synthetic musk odorants with nitro or polycyclic moieties or ester bonds activate distinct but nearby glomeruli. Anterodorsal bulbar lesions cause muscone anosmia, suggesting that this region is involved in muscone perception. Finally, we identified the mouse olfactory receptor, MOR215-1, that was a specific muscone receptor expressed by neurons innervating the muscone-responsive anteromedial glomeruli and also the human muscone receptor, OR5AN1. The current study documents the olfactory neural pathway in mice that senses and transmits musk signals from receptor to brain.
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan; ERATO Touhara Chemosensory Signal Project, JST, The University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Shirasu
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Yoshikawa
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Takai
authors.affiliation: Department of Brain Function, School of Medical Science, University of Fukui, Fukui 910-1193, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Nakashima
authors.affiliation: Department of Brain Function, School of Medical Science, University of Fukui, Fukui 910-1193, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Takeuchi
authors.affiliation: Department of Brain Function, School of Medical Science, University of Fukui, Fukui 910-1193, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sakano
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan; ERATO Touhara Chemosensory Signal Project, JST, The University of Tokyo, Tokyo 113-8657, Japan. Electronic address: ktouhara@mail.ecc.u-tokyo.ac.jp.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Touhara
mesh_terms: D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D003516:Cycloparaffins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005229:Fatty Acids, Monounsaturated; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D009812:Odorants; D009830:Olfactory Bulb / Q000166:cytology* / Q000601:surgery; D009833:Olfactory Pathways / Q000187:drug effects / Q000502:physiology*; D018034:Olfactory Receptor Neurons / Q000187:drug effects / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D018035:Receptors, Odorant / Q000235:genetics; D012903:Smell / Q000187:drug effects / Q000502:physiology*; D014982:Xenopus laevis
chemical_list: D003516:Cycloparaffins; D005229:Fatty Acids, Monounsaturated; C108768:Ncam2 protein, mouse; D019006:Neural Cell Adhesion Molecules; C122168:OR52A1 protein, human; D016760:Proto-Oncogene Proteins c-fos; D018035:Receptors, Odorant; C485184:enhanced green fluorescent protein; C008563:musk; D049452:Green Fluorescent Proteins; D005576:Colforsin; C031021:muscone