Carotid Body Function in Tyrosine Hydroxylase Conditional Olfr78 Knockout Mice

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...

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Authors: Colinas, Olalla, Mombaerts, Peter, López-Barneo, José, Ortega-Sáenz, Patricia
Format: article
Status:Published version
Publication Date:2024
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/368218
Online Access:http://hdl.handle.net/10261/368218
https://api.elsevier.com/content/abstract/scopus_id/85192609702
Access Level:Open access
Keyword:Responsiveness to hypoxia
Olfr78 knockout
Carotid body
Chemoreception
Glomus cells
Hypoxic ventilatory response
Neuroblasts
Olfactory receptor
Oxygen sensing
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spelling Carotid Body Function in Tyrosine Hydroxylase Conditional Olfr78 Knockout MiceColinas, OlallaMombaerts, PeterLópez-Barneo, JoséOrtega-Sáenz, PatriciaResponsiveness to hypoxiaOlfr78 knockoutCarotid bodyChemoreceptionGlomus cellsHypoxic ventilatory responseNeuroblastsOlfactory receptorOxygen sensingThe 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.This research was supported by the Spanish Ministries of Science and Innovation and Health [Grants SAF2016-74990-R and PID2019-106410RB-I00 funded by MCIN/AEI/10.13039/501100011033], and the European Research Council [ERC Advanced Grant PRJ201502629]. P.M. acknowledges the generous grant support from the Max Planck Society.Peer reviewedOxford University PressMinisterio de Ciencia e Innovación (España)Agencia Estatal de Investigación (España)European Research CouncilMax Planck SocietyConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/368218https://api.elsevier.com/content/abstract/scopus_id/85192609702reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI//SAF2016-74990-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-106410RB-I00The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1093/function/zqae010https://doi.org/10.1093/function/zqae010Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3682182026-05-22T06:33:51Z
dc.title.none.fl_str_mv Carotid Body Function in Tyrosine Hydroxylase Conditional Olfr78 Knockout Mice
title Carotid Body Function in Tyrosine Hydroxylase Conditional Olfr78 Knockout Mice
spellingShingle Carotid Body Function in Tyrosine Hydroxylase Conditional Olfr78 Knockout Mice
Colinas, Olalla
Responsiveness to hypoxia
Olfr78 knockout
Carotid body
Chemoreception
Glomus cells
Hypoxic ventilatory response
Neuroblasts
Olfactory receptor
Oxygen sensing
title_short Carotid Body Function in Tyrosine Hydroxylase Conditional Olfr78 Knockout Mice
title_full Carotid Body Function in Tyrosine Hydroxylase Conditional Olfr78 Knockout Mice
title_fullStr Carotid Body Function in Tyrosine Hydroxylase Conditional Olfr78 Knockout Mice
title_full_unstemmed Carotid Body Function in Tyrosine Hydroxylase Conditional Olfr78 Knockout Mice
title_sort Carotid Body Function in Tyrosine Hydroxylase Conditional Olfr78 Knockout Mice
dc.creator.none.fl_str_mv Colinas, Olalla
Mombaerts, Peter
López-Barneo, José
Ortega-Sáenz, Patricia
author Colinas, Olalla
author_facet Colinas, Olalla
Mombaerts, Peter
López-Barneo, José
Ortega-Sáenz, Patricia
author_role author
author2 Mombaerts, Peter
López-Barneo, José
Ortega-Sáenz, Patricia
author2_role author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Agencia Estatal de Investigación (España)
European Research Council
Max Planck Society
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Responsiveness to hypoxia
Olfr78 knockout
Carotid body
Chemoreception
Glomus cells
Hypoxic ventilatory response
Neuroblasts
Olfactory receptor
Oxygen sensing
topic Responsiveness to hypoxia
Olfr78 knockout
Carotid body
Chemoreception
Glomus cells
Hypoxic ventilatory response
Neuroblasts
Olfactory receptor
Oxygen sensing
description 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.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/368218
https://api.elsevier.com/content/abstract/scopus_id/85192609702
url http://hdl.handle.net/10261/368218
https://api.elsevier.com/content/abstract/scopus_id/85192609702
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI//SAF2016-74990-R
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-106410RB-I00
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1093/function/zqae010
https://doi.org/10.1093/function/zqae010
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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