Genetically engineered mice for combinatorial cardiovascular optobiology

Optogenetic effectors and sensors provide a novel real-time window into complex physiological processes, enabling determination of molecular signaling processes within functioning cellular networks. However, the combination of these optical tools in mice is made practical by construction of genetic...

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Autores principales:	Frank K Lee, Jane C Lee, Bo Shui, Shaun Reining, Megan Jibilian, David M Small, Jason S Jones, Nathaniel H Allan-Rahill, Michael RE Lamont, Megan A Rizzo, Sendoa Tajada, Manuel F Navedo, Luis Fernando Santana, Nozomi Nishimura, Michael I Kotlikoff
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	calcium imaging optogenetics imaging Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/1b8cb82950fd45838080d740449051eb
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spelling	oai:doaj.org-article:1b8cb82950fd45838080d740449051eb2021-11-16T14:24:15ZGenetically engineered mice for combinatorial cardiovascular optobiology10.7554/eLife.678582050-084Xe67858https://doaj.org/article/1b8cb82950fd45838080d740449051eb2021-10-01T00:00:00Zhttps://elifesciences.org/articles/67858https://doaj.org/toc/2050-084XOptogenetic effectors and sensors provide a novel real-time window into complex physiological processes, enabling determination of molecular signaling processes within functioning cellular networks. However, the combination of these optical tools in mice is made practical by construction of genetic lines that are optically compatible and genetically tractable. We present a new toolbox of 21 mouse lines with lineage-specific expression of optogenetic effectors and sensors for direct biallelic combination, avoiding the multiallelic requirement of Cre recombinase -mediated DNA recombination, focusing on models relevant for cardiovascular biology. Optogenetic effectors (11 lines) or Ca2+ sensors (10 lines) were selectively expressed in cardiac pacemaker cells, cardiomyocytes, vascular endothelial and smooth muscle cells, alveolar epithelial cells, lymphocytes, glia, and other cell types. Optogenetic effector and sensor function was demonstrated in numerous tissues. Arterial/arteriolar tone was modulated by optical activation of the second messengers InsP3 (optoα1AR) and cAMP (optoß2AR), or Ca2+-permeant membrane channels (CatCh2) in smooth muscle (Acta2) and endothelium (Cdh5). Cardiac activation was separately controlled through activation of nodal/conducting cells or cardiac myocytes. We demonstrate combined effector and sensor function in biallelic mouse crosses: optical cardiac pacing and simultaneous cardiomyocyte Ca2+ imaging in Hcn4BAC-CatCh2/Myh6-GCaMP8 crosses. These experiments highlight the potential of these mice to explore cellular signaling in vivo, in complex tissue networks.Frank K LeeJane C LeeBo ShuiShaun ReiningMegan JibilianDavid M SmallJason S JonesNathaniel H Allan-RahillMichael RE LamontMegan A RizzoSendoa TajadaManuel F NavedoLuis Fernando SantanaNozomi NishimuraMichael I KotlikoffeLife Sciences Publications Ltdarticlecalcium imagingoptogeneticsimagingMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	calcium imaging optogenetics imaging Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	calcium imaging optogenetics imaging Medicine R Science Q Biology (General) QH301-705.5 Frank K Lee Jane C Lee Bo Shui Shaun Reining Megan Jibilian David M Small Jason S Jones Nathaniel H Allan-Rahill Michael RE Lamont Megan A Rizzo Sendoa Tajada Manuel F Navedo Luis Fernando Santana Nozomi Nishimura Michael I Kotlikoff Genetically engineered mice for combinatorial cardiovascular optobiology
description	Optogenetic effectors and sensors provide a novel real-time window into complex physiological processes, enabling determination of molecular signaling processes within functioning cellular networks. However, the combination of these optical tools in mice is made practical by construction of genetic lines that are optically compatible and genetically tractable. We present a new toolbox of 21 mouse lines with lineage-specific expression of optogenetic effectors and sensors for direct biallelic combination, avoiding the multiallelic requirement of Cre recombinase -mediated DNA recombination, focusing on models relevant for cardiovascular biology. Optogenetic effectors (11 lines) or Ca2+ sensors (10 lines) were selectively expressed in cardiac pacemaker cells, cardiomyocytes, vascular endothelial and smooth muscle cells, alveolar epithelial cells, lymphocytes, glia, and other cell types. Optogenetic effector and sensor function was demonstrated in numerous tissues. Arterial/arteriolar tone was modulated by optical activation of the second messengers InsP3 (optoα1AR) and cAMP (optoß2AR), or Ca2+-permeant membrane channels (CatCh2) in smooth muscle (Acta2) and endothelium (Cdh5). Cardiac activation was separately controlled through activation of nodal/conducting cells or cardiac myocytes. We demonstrate combined effector and sensor function in biallelic mouse crosses: optical cardiac pacing and simultaneous cardiomyocyte Ca2+ imaging in Hcn4BAC-CatCh2/Myh6-GCaMP8 crosses. These experiments highlight the potential of these mice to explore cellular signaling in vivo, in complex tissue networks.
format	article
author	Frank K Lee Jane C Lee Bo Shui Shaun Reining Megan Jibilian David M Small Jason S Jones Nathaniel H Allan-Rahill Michael RE Lamont Megan A Rizzo Sendoa Tajada Manuel F Navedo Luis Fernando Santana Nozomi Nishimura Michael I Kotlikoff
author_facet	Frank K Lee Jane C Lee Bo Shui Shaun Reining Megan Jibilian David M Small Jason S Jones Nathaniel H Allan-Rahill Michael RE Lamont Megan A Rizzo Sendoa Tajada Manuel F Navedo Luis Fernando Santana Nozomi Nishimura Michael I Kotlikoff
author_sort	Frank K Lee
title	Genetically engineered mice for combinatorial cardiovascular optobiology
title_short	Genetically engineered mice for combinatorial cardiovascular optobiology
title_full	Genetically engineered mice for combinatorial cardiovascular optobiology
title_fullStr	Genetically engineered mice for combinatorial cardiovascular optobiology
title_full_unstemmed	Genetically engineered mice for combinatorial cardiovascular optobiology
title_sort	genetically engineered mice for combinatorial cardiovascular optobiology
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/1b8cb82950fd45838080d740449051eb
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_version_	1718426345167388672

Genetically engineered mice for combinatorial cardiovascular optobiology

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