{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T17:53:36Z","timestamp":1781632416080,"version":"3.54.5"},"reference-count":49,"publisher":"American Physiological Society","issue":"3","license":[{"start":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T00:00:00Z","timestamp":1708560000000},"content-version":"vor","delay-in-days":52,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["PRJ201502629"],"award-info":[{"award-number":["PRJ201502629"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The Olfr78 gene encodes a G-protein-coupled olfactory receptor that is expressed in several ectopic sites. Olfr78 is one of the most abundant mRNA species in carotid body (CB) glomus cells. These cells are the prototypical oxygen (O2) sensitive arterial chemoreceptors, which, in response to lowered O2 tension (hypoxia), activate the respiratory centers to induce hyperventilation. It has been proposed that Olfr78 is a lactate receptor and that glomus cell activation by the increase in blood lactate mediates the hypoxic ventilatory response (HVR). However, this proposal has been challenged by several groups showing that Olfr78 is not a physiologically relevant lactate receptor and that the O2-based regulation of breathing is not affected in constitutive Olfr78 knockout mice. In another study, constitutive Olfr78 knockout mice were reported to have altered systemic and CB responses to mild hypoxia. To further characterize the functional role of Olfr78 in CB glomus cells, we here generated a conditional Olfr78 knockout mouse strain and then restricted the knockout to glomus cells and other catecholaminergic cells by crossing with a tyrosine hydroxylase-specific Cre driver strain (TH-Olfr78 KO mice). We find that TH-Olfr78 KO mice have a normal HVR. Interestingly, glomus cells of TH-Olfr78 KO mice exhibit molecular and electrophysiological alterations as well as a reduced dopamine content in secretory vesicles and neurosecretory activity. These functional characteristics resemble those of CB neuroblasts in wild-type mice. We suggest that, although Olfr78 is not essential for CB O2 sensing, activation of Olfr78-dependent pathways is required for maturation of glomus cells.<\/jats:p>","DOI":"10.1093\/function\/zqae010","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T10:02:49Z","timestamp":1708509769000},"source":"Crossref","is-referenced-by-count":10,"title":["Carotid Body Function in Tyrosine Hydroxylase Conditional Olfr78 Knockout Mice"],"prefix":"10.1152","volume":"5","author":[{"given":"Olalla","family":"Colinas","sequence":"first","affiliation":[{"name":"Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla , Sevile 41013, Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Facultad de Medicina, Universidad de Sevilla , Seville 41009, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) , Sevile 41013, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Mombaerts","sequence":"additional","affiliation":[{"name":"Max Planck Research Unit for Neurogenetics , Frankfurt 60438 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"L\u00f3pez-Barneo","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla , Sevile 41013, Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Facultad de Medicina, Universidad de Sevilla , Seville 41009, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) , Sevile 41013, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Ortega-S\u00e1enz","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla , Sevile 41013, Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Facultad de Medicina, Universidad de Sevilla , Seville 41009, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) , Sevile 41013, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","published-online":{"date-parts":[[2024,2,22]]},"reference":[{"issue":"7577","key":"2024050216463770300_bib1","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/nature15721","article-title":"Oxygen regulation of breathing through an olfactory receptor activated by lactate","volume":"527","author":"Chang","year":"2015","journal-title":"Nature"},{"issue":"15","key":"2024050216463770300_bib2","doi-asserted-by":"crossref","first-page":"4225","DOI":"10.1113\/JP271936","article-title":"Single cell transcriptome analysis of mouse carotid body glomus cells","volume":"594","author":"Zhou","year":"2016","journal-title":"J Physiol"},{"issue":"18","key":"2024050216463770300_bib3","doi-asserted-by":"crossref","first-page":"6091","DOI":"10.1113\/JP274684","article-title":"Gene expression analyses reveal metabolic specifications in acute O2-sensing chemoreceptor cells","volume":"595","author":"Gao","year":"2017","journal-title":"J Physiol"},{"issue":"1","key":"2024050216463770300_bib4","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1146\/annurev-physiol-020518-114427","article-title":"Physiology of the carotid body: from molecules to disease","volume":"82","author":"Ortega-Saenz","year":"2020","journal-title":"Annu Rev Physiol"},{"issue":"3","key":"2024050216463770300_bib5","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1152\/physrev.00039.2019","article-title":"Carotid body chemoreceptors: physiology, pathology, and implications for health and disease","volume":"101","author":"Iturriaga","year":"2021","journal-title":"Physiol Rev"},{"issue":"1","key":"2024050216463770300_bib6","doi-asserted-by":"crossref","first-page":"38231","DOI":"10.1038\/srep38231","article-title":"Defining an olfactory receptor function in airway smooth muscle cells","volume":"6","author":"Aisenberg","year":"2016","journal-title":"Sci Rep"},{"issue":"7724","key":"2024050216463770300_bib7","doi-asserted-by":"crossref","first-page":"E33","DOI":"10.1038\/s41586-018-0545-9","article-title":"The role of Olfr78 in the breathing circuit of mice","volume":"561","author":"Torres-Torrelo","year":"2018","journal-title":"Nature"},{"issue":"5","key":"2024050216463770300_bib8","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1152\/jn.00075.2020","article-title":"Olfactory receptor 78 participates in carotid body response to a wide range of low O(2) levels but not severe hypoxia","volume":"123","author":"Peng","year":"2020","journal-title":"J Neurophysiol"},{"issue":"4865","key":"2024050216463770300_bib9","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1126\/science.2456613","article-title":"Chemotransduction in the carotid body: K+ current modulated by PO2 in type I chemoreceptor cells","volume":"241","author":"Lopez-Barneo","year":"1988","journal-title":"Science"},{"issue":"3","key":"2024050216463770300_bib10","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1113\/jphysiol.1994.sp020143","article-title":"Effects of hypoxia on membrane potential and intracellular calcium in rat neonatal carotid body type I cells","volume":"476","author":"Buckler","year":"1994","journal-title":"J Physiol"},{"issue":"21","key":"2024050216463770300_bib11","doi-asserted-by":"crossref","first-page":"10208","DOI":"10.1073\/pnas.91.21.10208","article-title":"Hypoxia induces voltage-dependent Ca2+ entry and quantal dopamine secretion in carotid body glomus cells","volume":"91","author":"Urena","year":"1994","journal-title":"Proc Natl Acad Sci USA"},{"issue":"1","key":"2024050216463770300_bib12","doi-asserted-by":"crossref","first-page":"4166","DOI":"10.1038\/s41467-021-24444-7","article-title":"Lactate sensing mechanisms in arterial chemoreceptor cells","volume":"12","author":"Torres-Torrelo","year":"2021","journal-title":"Nat Commun"},{"issue":"6","key":"2024050216463770300_bib13","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1152\/jn.00067.2021","article-title":"Role of olfactory receptor78 in carotid body-dependent sympathetic activation and hypertension in murine models of chronic intermittent hypoxia","volume":"125","author":"Peng","year":"2021","journal-title":"J Neurophysiol"},{"issue":"615","key":"2024050216463770300_bib14","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.aay9452","article-title":"Acute O2 sensing through HIF2alpha-dependent expression of atypical cytochrome oxidase subunits in arterial chemoreceptors","volume":"13","author":"Moreno-Dominguez","year":"2020","journal-title":"Sci Signal"},{"key":"2024050216463770300_bib15","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/978-3-031-32371-3_17","article-title":"Constitutive expression of Hif2alpha confers acute O(2) sensitivity to carotid body glomus cells","volume":"1427","author":"Colinas","year":"2023","journal-title":"Adv Exp Med Biol"},{"issue":"2","key":"2024050216463770300_bib16","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.neuron.2008.11.010","article-title":"Mapping of class I and class II odorant receptors to glomerular domains by two distinct types of olfactory sensory neurons in the mouse","volume":"61","author":"Bozza","year":"2009","journal-title":"Neuron"},{"issue":"3","key":"2024050216463770300_bib17","doi-asserted-by":"crossref","DOI":"10.15252\/embr.201744598","article-title":"Fast neurogenesis from carotid body quiescent neuroblasts accelerates adaptation to hypoxia","volume":"19","author":"Sobrino","year":"2018","journal-title":"EMBO Rep"},{"issue":"2","key":"2024050216463770300_bib18","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/gene.20065","article-title":"Transgenic expression of Cre recombinase from the tyrosine hydroxylase locus","volume":"40","author":"Lindeberg","year":"2004","journal-title":"Genesis"},{"issue":"5","key":"2024050216463770300_bib19","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.cmet.2015.09.004","article-title":"Oxygen sensing by arterial chemoreceptors depends on mitochondrial complex I signaling","volume":"22","author":"Fernandez-Aguera","year":"2015","journal-title":"Cell Metab"},{"issue":"39","key":"2024050216463770300_bib20","doi-asserted-by":"crossref","first-page":"e2202178119","DOI":"10.1073\/pnas.2202178119","article-title":"Oxygen regulation of breathing is abolished in mitochondrial complex III-deficient arterial chemoreceptors","volume":"119","author":"Cabello-Rivera","year":"2022","journal-title":"Proc Natl Acad Sci USA"},{"issue":"7","key":"2024050216463770300_bib21","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1073\/pnas.0608382104","article-title":"Acute postnatal ablation of hif-2alpha results in anemia","volume":"104","author":"Gruber","year":"2007","journal-title":"Proc Natl Acad Sci USA"},{"issue":"2","key":"2024050216463770300_bib22","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1006\/dbio.2002.0597","article-title":"Efficient recombination in diverse tissues by a tamoxifen-inducible form of Cre: a tool for temporally regulated gene activation\/inactivation in the mouse","volume":"244","author":"Hayashi","year":"2002","journal-title":"Dev Biol"},{"key":"2024050216463770300_bib23","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/978-1-4939-7665-2_13","article-title":"Testing acute oxygen sensing in genetically modified mice: plethysmography and amperometry","volume":"1742","author":"Ortega-Saenz","year":"2018","journal-title":"Methods Mol Biol"},{"key":"2024050216463770300_bib24","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/978-1-4939-7665-2_12","article-title":"Monitoring functional responses to hypoxia in single carotid body cells","volume":"1742","author":"Munoz-Cabello","year":"2018","journal-title":"Methods Mol Biol"},{"issue":"4","key":"2024050216463770300_bib25","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1085\/jgp.200910302","article-title":"Carotid body chemosensory responses in mice deficient of TASK channels","volume":"135","author":"Ortega-Saenz","year":"2010","journal-title":"J Gen Physiol"},{"issue":"2","key":"2024050216463770300_bib26","doi-asserted-by":"crossref","first-page":"100535","DOI":"10.1016\/j.xpro.2021.100535","article-title":"Using redox-sensitive fluorescent probes to record real-time reactive oxygen species production in cells from mouse carotid body slices","volume":"2","author":"Gao","year":"2021","journal-title":"STAR Protocols"},{"issue":"4","key":"2024050216463770300_bib27","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1085\/jgp.200609591","article-title":"Acute oxygen sensing in heme oxygenase-2 null mice","volume":"128","author":"Ortega-Saenz","year":"2006","journal-title":"J Gen Physiol"},{"key":"2024050216463770300_bib28","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.78915","article-title":"Tissue-specific mitochondrial HIGD1C promotes oxygen sensitivity in carotid body chemoreceptors","volume":"11","author":"Timon-Gomez","year":"2022","journal-title":"eLife"},{"key":"2024050216463770300_bib29","doi-asserted-by":"publisher","DOI":"10.1101\/2023.07.14.548982","article-title":"Hif-2\u03b1 programmes oxygen chemosensitivity in chromaffin cells","author":"Prange-Barczynska","year":"2023","journal-title":"bioRxiv 2023.07.14.548982"},{"key":"2024050216463770300_bib30","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/B978-0-323-91534-2.00010-2","article-title":"Neurobiology of the carotid body","volume":"188","author":"Lopez-Barneo","year":"2022","journal-title":"Handb Clin Neurol"},{"issue":"1-2","key":"2024050216463770300_bib31","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.cell.2013.12.013","article-title":"An O2-sensitive glomus cell-stem cell synapse induces carotid body growth in chronic hypoxia","volume":"156","author":"Platero-Luengo","year":"2014","journal-title":"Cell"},{"issue":"2","key":"2024050216463770300_bib32","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.cell.2007.07.043","article-title":"Glia-like stem cells sustain physiologic neurogenesis in the adult mammalian carotid body","volume":"131","author":"Pardal","year":"2007","journal-title":"Cell"},{"issue":"5","key":"2024050216463770300_bib33","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1085\/jgp.93.5.979","article-title":"Ionic currents in dispersed chemoreceptor cells of the mammalian carotid body","volume":"93","author":"Urena","year":"1989","journal-title":"J Gen Physiol"},{"issue":"Pt 3","key":"2024050216463770300_bib34","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1113\/jphysiol.1995.sp021083","article-title":"L- and N-type Ca2+ channels in adult rat carotid body chemoreceptor type I cells","volume":"489","author":"e\u00a0Silva","year":"1995","journal-title":"J Physiol"},{"issue":"1","key":"2024050216463770300_bib35","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1152\/jn.00775.2015","article-title":"CaV3.2 T-type Ca2+ channels mediate the augmented calcium influx in carotid body glomus cells by chronic intermittent hypoxia","volume":"115","author":"Makarenko","year":"2016","journal-title":"J Neurophysiol"},{"issue":"2","key":"2024050216463770300_bib36","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1002\/jnr.10164","article-title":"Olfactory receptor expressed in ganglia of the autonomic nervous system","volume":"68","author":"Weber","year":"2002","journal-title":"J Neurosci Res"},{"issue":"11","key":"2024050216463770300_bib37","doi-asserted-by":"crossref","first-page":"4410","DOI":"10.1073\/pnas.1215927110","article-title":"Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation","volume":"110","author":"Pluznick","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"issue":"3","key":"2024050216463770300_bib38","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1007\/s00441-015-2165-0","article-title":"Expression of odorant receptor Olfr78 in enteroendocrine cells of the colon","volume":"361","author":"Fleischer","year":"2015","journal-title":"Cell Tissue Res"},{"issue":"2","key":"2024050216463770300_bib39","first-page":"237","article-title":"Acetate enhances the chemosensory response to hypoxia in the cat carotid body in vitro in the absence of CO2-HCO3","volume":"29","author":"Iturriaga","year":"1996","journal-title":"Biol Res"},{"issue":"5","key":"2024050216463770300_bib40","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1113\/JP283897","article-title":"Rearrangement of cell types in the rat carotid body neurogenic niche induced by chronic intermittent hypoxia","volume":"601","author":"Caballero-Eraso","year":"2023","journal-title":"J Physiol"},{"issue":"15","key":"2024050216463770300_bib41","doi-asserted-by":"crossref","first-page":"3259","DOI":"10.1002\/jnr.21938","article-title":"Voltage-operated Ca(2+) and Na(+) channels in the oligodendrocyte lineage","volume":"87","author":"Paez","year":"2009","journal-title":"J Neurosci Res"},{"issue":"7","key":"2024050216463770300_bib42","doi-asserted-by":"crossref","first-page":"4483","DOI":"10.4049\/jimmunol.0803003","article-title":"Developmental switch of the expression of ion channels in human dendritic cells","volume":"183","author":"Zsiros","year":"2009","journal-title":"J Immunol"},{"key":"2024050216463770300_bib43","article-title":"Canales de calcio de las c\u00e9lulas gl\u00f3micas y su modulaci\u00f3n por dopamina","volume-title":"PhD Thesis","author":"Rodriguez\u00a0Benot","year":"1991"},{"issue":"3","key":"2024050216463770300_bib44","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.mcn.2003.10.010","article-title":"Tyrosine hydroxylase transcription depends primarily on cAMP response element activity, regardless of the type of inducing stimulus","volume":"25","author":"Lewis-Tuffin","year":"2004","journal-title":"Mol Cell Neurosci"},{"issue":"5","key":"2024050216463770300_bib45","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1111\/j.1471-4159.2007.04468.x","article-title":"Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates the oxygen sensing type I (glomus) cells of rat carotid bodies via reduction of a background TASK-like K+ current","volume":"101","author":"Xu","year":"2007","journal-title":"J Neurochem"},{"issue":"27","key":"2024050216463770300_bib46","doi-asserted-by":"crossref","first-page":"eadf3026","DOI":"10.1126\/sciadv.adf3026","article-title":"Hypoxia sensing requires H(2)S-dependent persulfidation of olfactory receptor 78","volume":"9","author":"Peng","year":"2023","journal-title":"Sci Adv"},{"issue":"2","key":"2024050216463770300_bib47","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.pharmthera.2008.07.005","article-title":"Constitutive activation of G protein-coupled receptors and diseases: insights into mechanisms of activation and therapeutics","volume":"120","author":"Tao","year":"2008","journal-title":"Pharmacol Ther"},{"issue":"5","key":"2024050216463770300_bib48","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1172\/JCI133194","article-title":"Marked and rapid effects of pharmacological HIF-2alpha antagonism on hypoxic ventilatory control","volume":"130","author":"Cheng","year":"2020","journal-title":"J Clin Invest"},{"issue":"1","key":"2024050216463770300_bib49","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s11912-019-0752-z","article-title":"HIF inhibitors: status of current clinical development","volume":"21","author":"Fallah","year":"2019","journal-title":"Curr Oncol Rep"}],"container-title":["Function"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/full\/10.1093\/function\/zqae010","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1093\/function\/zqae010","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T17:07:10Z","timestamp":1781629630000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/full\/10.1093\/function\/zqae010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024]]},"references-count":49,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,5,2]]}},"URL":"https:\/\/doi.org\/10.1093\/function\/zqae010","relation":{},"ISSN":["2633-8823"],"issn-type":[{"value":"2633-8823","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024]]},"published":{"date-parts":[[2024]]},"article-number":"zqae010"}}