A RhoA-FRET Biosensor Mouse for Intravital Imaging in Normal Tissue Homeostasis and Disease Contexts
The small GTPase RhoA is involved in a variety of fundamental processes in normal tissue. Spatiotemporal control of RhoA is thought to govern mechanosensing, growth, and motility of cells, while its deregulation is associated with disease development. Here, we describe the generation of a RhoA-fluor...
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Elsevier
2017-10-01
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Series: | Cell Reports |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717312974 |
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DOAJ |
language |
English |
format |
Article |
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DOAJ |
author |
Max Nobis David Herrmann Sean C. Warren Shereen Kadir Wilfred Leung Monica Killen Astrid Magenau David Stevenson Morghan C. Lucas Nadine Reischmann Claire Vennin James R.W. Conway Alice Boulghourjian Anaiis Zaratzian Andrew M. Law David Gallego-Ortega Christopher J. Ormandy Stacey N. Walters Shane T. Grey Jacqueline Bailey Tatyana Chtanova Julian M.W. Quinn Paul A. Baldock Peter I. Croucher Juliane P. Schwarz Agata Mrowinska Lei Zhang Herbert Herzog Andrius Masedunskas Edna C. Hardeman Peter W. Gunning Gonzalo del Monte-Nieto Richard P. Harvey Michael S. Samuel Marina Pajic Ewan J. McGhee Anna-Karin E. Johnsson Owen J. Sansom Heidi C.E. Welch Jennifer P. Morton Douglas Strathdee Kurt I. Anderson Paul Timpson |
spellingShingle |
Max Nobis David Herrmann Sean C. Warren Shereen Kadir Wilfred Leung Monica Killen Astrid Magenau David Stevenson Morghan C. Lucas Nadine Reischmann Claire Vennin James R.W. Conway Alice Boulghourjian Anaiis Zaratzian Andrew M. Law David Gallego-Ortega Christopher J. Ormandy Stacey N. Walters Shane T. Grey Jacqueline Bailey Tatyana Chtanova Julian M.W. Quinn Paul A. Baldock Peter I. Croucher Juliane P. Schwarz Agata Mrowinska Lei Zhang Herbert Herzog Andrius Masedunskas Edna C. Hardeman Peter W. Gunning Gonzalo del Monte-Nieto Richard P. Harvey Michael S. Samuel Marina Pajic Ewan J. McGhee Anna-Karin E. Johnsson Owen J. Sansom Heidi C.E. Welch Jennifer P. Morton Douglas Strathdee Kurt I. Anderson Paul Timpson A RhoA-FRET Biosensor Mouse for Intravital Imaging in Normal Tissue Homeostasis and Disease Contexts Cell Reports intravital imaging pancreatic cancer breast cancer actin small GTPase RhoA FLIM-FRET biosensors immunology development cell biology |
author_facet |
Max Nobis David Herrmann Sean C. Warren Shereen Kadir Wilfred Leung Monica Killen Astrid Magenau David Stevenson Morghan C. Lucas Nadine Reischmann Claire Vennin James R.W. Conway Alice Boulghourjian Anaiis Zaratzian Andrew M. Law David Gallego-Ortega Christopher J. Ormandy Stacey N. Walters Shane T. Grey Jacqueline Bailey Tatyana Chtanova Julian M.W. Quinn Paul A. Baldock Peter I. Croucher Juliane P. Schwarz Agata Mrowinska Lei Zhang Herbert Herzog Andrius Masedunskas Edna C. Hardeman Peter W. Gunning Gonzalo del Monte-Nieto Richard P. Harvey Michael S. Samuel Marina Pajic Ewan J. McGhee Anna-Karin E. Johnsson Owen J. Sansom Heidi C.E. Welch Jennifer P. Morton Douglas Strathdee Kurt I. Anderson Paul Timpson |
author_sort |
Max Nobis |
title |
A RhoA-FRET Biosensor Mouse for Intravital Imaging in Normal Tissue Homeostasis and Disease Contexts |
title_short |
A RhoA-FRET Biosensor Mouse for Intravital Imaging in Normal Tissue Homeostasis and Disease Contexts |
title_full |
A RhoA-FRET Biosensor Mouse for Intravital Imaging in Normal Tissue Homeostasis and Disease Contexts |
title_fullStr |
A RhoA-FRET Biosensor Mouse for Intravital Imaging in Normal Tissue Homeostasis and Disease Contexts |
title_full_unstemmed |
A RhoA-FRET Biosensor Mouse for Intravital Imaging in Normal Tissue Homeostasis and Disease Contexts |
title_sort |
rhoa-fret biosensor mouse for intravital imaging in normal tissue homeostasis and disease contexts |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2017-10-01 |
description |
The small GTPase RhoA is involved in a variety of fundamental processes in normal tissue. Spatiotemporal control of RhoA is thought to govern mechanosensing, growth, and motility of cells, while its deregulation is associated with disease development. Here, we describe the generation of a RhoA-fluorescence resonance energy transfer (FRET) biosensor mouse and its utility for monitoring real-time activity of RhoA in a variety of native tissues in vivo. We assess changes in RhoA activity during mechanosensing of osteocytes within the bone and during neutrophil migration. We also demonstrate spatiotemporal order of RhoA activity within crypt cells of the small intestine and during different stages of mammary gestation. Subsequently, we reveal co-option of RhoA activity in both invasive breast and pancreatic cancers, and we assess drug targeting in these disease settings, illustrating the potential for utilizing this mouse to study RhoA activity in vivo in real time. |
topic |
intravital imaging pancreatic cancer breast cancer actin small GTPase RhoA FLIM-FRET biosensors immunology development cell biology |
url |
http://www.sciencedirect.com/science/article/pii/S2211124717312974 |
work_keys_str_mv |
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doaj-c83a8ae4b29e4df59cdaacb8bc5a58022020-11-25T01:39:04ZengElsevierCell Reports2211-12472017-10-0121127428810.1016/j.celrep.2017.09.022A RhoA-FRET Biosensor Mouse for Intravital Imaging in Normal Tissue Homeostasis and Disease ContextsMax Nobis0David Herrmann1Sean C. Warren2Shereen Kadir3Wilfred Leung4Monica Killen5Astrid Magenau6David Stevenson7Morghan C. Lucas8Nadine Reischmann9Claire Vennin10James R.W. Conway11Alice Boulghourjian12Anaiis Zaratzian13Andrew M. Law14David Gallego-Ortega15Christopher J. Ormandy16Stacey N. Walters17Shane T. Grey18Jacqueline Bailey19Tatyana Chtanova20Julian M.W. Quinn21Paul A. Baldock22Peter I. Croucher23Juliane P. Schwarz24Agata Mrowinska25Lei Zhang26Herbert Herzog27Andrius Masedunskas28Edna C. Hardeman29Peter W. Gunning30Gonzalo del Monte-Nieto31Richard P. Harvey32Michael S. Samuel33Marina Pajic34Ewan J. McGhee35Anna-Karin E. Johnsson36Owen J. Sansom37Heidi C.E. Welch38Jennifer P. Morton39Douglas Strathdee40Kurt I. Anderson41Paul Timpson42The Garvan Institute of Medical Research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, AustraliaThe Garvan Institute of Medical Research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, AustraliaThe Garvan Institute of Medical Research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, AustraliaCancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G611BD, UKThe Garvan Institute of Medical Research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, AustraliaThe Garvan Institute of Medical Research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, AustraliaThe Garvan Institute of Medical Research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, AustraliaCancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G611BD, UKThe Garvan Institute of Medical Research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, AustraliaThe Garvan Institute of Medical Research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, AustraliaThe Garvan Institute of Medical Research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, AustraliaThe Garvan Institute of Medical Research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, AustraliaThe Garvan Institute of Medical Research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, AustraliaThe Garvan Institute of Medical Research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, AustraliaThe Garvan Institute of Medical Research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, AustraliaThe Garvan Institute of Medical Research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, AustraliaThe Garvan Institute of Medical Research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, AustraliaThe Garvan Institute of Medical Research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, AustraliaThe Garvan Institute of Medical Research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, AustraliaThe Garvan Institute of Medical Research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, AustraliaThe Garvan Institute of Medical Research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, AustraliaThe Garvan Institute of Medical Research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, AustraliaThe Garvan Institute of Medical Research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, AustraliaThe Garvan Institute of Medical Research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, AustraliaCancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G611BD, UKCancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G611BD, UKThe Garvan Institute of Medical Research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, AustraliaThe Garvan Institute of Medical Research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, AustraliaNeuromuscular and Regenerative Medicine Unit, University of New South Wales, Sydney, NSW 2010, AustraliaNeuromuscular and Regenerative Medicine Unit, University of New South Wales, Sydney, NSW 2010, AustraliaOncology Research Unit, School of Medical Sciences, University of New South Wales, Sydney, NSW 2010, AustraliaDevelopmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Sydney, NSW 2010, AustraliaDevelopmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Sydney, NSW 2010, AustraliaCentre for Cancer Biology, SA Pathology and University of South Australia School of Medicine, University of Adelaide, Adelaide, SA 5000, AustraliaThe Garvan Institute of Medical Research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, AustraliaCancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G611BD, UKSignalling Programme, Babraham Institute, Cambridge CB223AT, UKCancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G611BD, UKSignalling Programme, Babraham Institute, Cambridge CB223AT, UKCancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G611BD, UKCancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G611BD, UKFrancis Crick Institute, London NW11AT, UKThe Garvan Institute of Medical Research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, AustraliaThe small GTPase RhoA is involved in a variety of fundamental processes in normal tissue. Spatiotemporal control of RhoA is thought to govern mechanosensing, growth, and motility of cells, while its deregulation is associated with disease development. Here, we describe the generation of a RhoA-fluorescence resonance energy transfer (FRET) biosensor mouse and its utility for monitoring real-time activity of RhoA in a variety of native tissues in vivo. We assess changes in RhoA activity during mechanosensing of osteocytes within the bone and during neutrophil migration. We also demonstrate spatiotemporal order of RhoA activity within crypt cells of the small intestine and during different stages of mammary gestation. Subsequently, we reveal co-option of RhoA activity in both invasive breast and pancreatic cancers, and we assess drug targeting in these disease settings, illustrating the potential for utilizing this mouse to study RhoA activity in vivo in real time.http://www.sciencedirect.com/science/article/pii/S2211124717312974intravital imagingpancreatic cancerbreast canceractinsmall GTPase RhoAFLIM-FRETbiosensorsimmunologydevelopmentcell biology |