title: Partial rescue of taste responses of alpha-gustducin null mice by transgenic expression of alpha-transducin.
abstract: The transduction of responses to bitter and sweet compounds utilizes guanine nucleotide binding proteins (G proteins) and their coupled receptors. Alpha-gustducin, a transducin-like G protein alpha-subunit, and rod alpha-transducin are expressed in taste receptor cells. Alpha-gustducin knockout mice have profoundly diminished behavioral and electrophysiological responses to many bitter and sweet compounds, although these mice retain residual responses to these compounds. Alpha-gustducin and rod alpha-transducin are biochemically indistinguishable in their in vitro interactions with retinal phosphodiesterase, rhodopsin and G protein betagamma-subunits. To determine if alpha-transducin can function in taste receptor cells and to compare the function of alpha-gustducin versus alpha-transducin in taste transduction in vivo, we generated transgenic mice that express alpha-transducin under the control of the alpha-gustducin promoter in the alpha-gustducin null background. Immunohistochemistry showed that the alpha-transducin transgene was expressed in about two-thirds of the alpha-gustducin lineage of taste receptor cells. Two-bottle preference tests showed that transgenic expression of rod alpha-transducin partly rescued responses to denatonium benzoate, sucrose and the artificial sweetener SC45647, but not to quinine sulfate. Gustatory nerve recordings showed a partial rescue by the transgene of the response to sucrose, SC45647 and quinine, but not to denatonium. These results demonstrate that alpha-transducin can function in taste receptor cells and transduce some taste cell responses. Our results also suggest that alpha-transducin and alpha-gustducin may differ, at least in part, in their function in these cells, although this conclusion must be qualified because of the limited fidelity of the transgene expression.
authors.affiliation: Department of Physiology and Biophysics, Howard Hughes Medical Institute, Mount Sinai School of Medicine, 1425 Madison Avenue, Box 1677, New York, NY 10029, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.forename: Vicktoria
authors.initials: V
authors.lastname: Danilova
authors.forename: Shiying
authors.initials: S
authors.lastname: Zou
authors.forename: Göran
authors.initials: G
authors.lastname: Hellekant
authors.forename: Marianna
authors.initials: M
authors.lastname: Max
authors.forename: Robert F
authors.initials: RF
authors.lastname: Margolskee
authors.forename: Sami
authors.initials: S
authors.lastname: Damak
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D049452:Green Fluorescent Proteins; D006146:Guanidines / Q000494:pharmacology; D007150:Immunohistochemistry; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D011803:Quinine / Q000494:pharmacology; D013395:Sucrose / Q000494:pharmacology; D013549:Sweetening Agents / Q000494:pharmacology; D013649:Taste / Q000235:genetics / Q000502:physiology*; D013650:Taste Buds / Q000502:physiology; D015293:Transducin / Q000235:genetics / Q000502:physiology*; D019076:Transgenes
chemical_list: D018712:Analgesics, Non-Narcotic; D049452:Green Fluorescent Proteins; D006146:Guanidines; D008164:Luminescent Proteins; D000644:Quaternary Ammonium Compounds; D011803:Quinine; D013395:Sucrose; D013549:Sweetening Agents; D015293:Transducin; C099860:SC 45647; C075192:gustducin; C043414:denatonium