title: Virus-Mediated Expression of DREADDs for In Vivo Metabolic Studies.
abstract: During the past few years, CNO-sensitive designer G protein-coupled receptors (GPCRs) known as DREADDs (designer receptors exclusively activated by designer drugs) have emerged as powerful new tools for the study of GPCR physiology. In this chapter, we present protocols employing adeno-associated viruses (AAVs) to express a Gq-coupled DREADD (Dq) in two metabolically important cell types, AgRP neurons of the hypothalamus and hepatocytes of the liver. We also provide examples dealing with the metabolic analysis of the Dq mutant mice after administration of CNO in vivo. The approaches described in this chapter can be applied to other members of the DREADD family and, of course, different cell types. It is likely that the use of DREADD technology will identify physiologically important signaling pathways that can be targeted for therapeutic purposes.
authors.affiliation: Molecular Signaling Section, Laboratory of Bioorganic Chemistry, NIH-NIDDK, Bethesda, MD, 20892, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Rossi
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Cui
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Nakajima
authors.forename: Jianxin
authors.initials: J
authors.lastname: Hu
authors.forename: Lu
authors.initials: L
authors.lastname: Zhu
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wess
mesh_terms: D054369:Agouti-Related Protein / Q000378:metabolism; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology; D001786:Blood Glucose / Q000378:metabolism; D003024:Clozapine / Q000031:analogs & derivatives / Q000494:pharmacology; D000229:Dependovirus / Q000235:genetics*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D015870:Gene Expression; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D015202:Protein Engineering / Q000379:methods*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism*; D014771:Virion / Q000235:genetics
chemical_list: D054369:Agouti-Related Protein; D001786:Blood Glucose; D043562:Receptors, G-Protein-Coupled; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D003024:Clozapine; C079149:clozapine N-oxide