Monitoring AKT activity and targeting in live tissue and disease contexts using a real-time Akt-FRET biosensor mouse
Aberrant AKT activation occurs in a number of cancers, metabolic syndrome, and immune disorders, making it an important target for the treatment of many diseases. To monitor spatial and temporal AKT activity in a live setting, we generated an Akt-FRET biosensor mouse that allows longitudinal assessm...
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| Veröffentlicht in: | Science advances 2023-04, Vol.9 (17), p.eadf9063 |
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| creator | Conway, James R W Warren, Sean C Lee, Young-Kyung McCulloch, Andrew T Magenau, Astrid Lee, Victoria Metcalf, Xanthe L Stoehr, Janett Haigh, Katharina Abdulkhalek, Lea Guaman, Cristian S Reed, Daniel A Murphy, Kendelle J Pereira, Brooke A Mélénec, Pauline Chambers, Cecilia Latham, Sharissa L Lenthall, Helen Deenick, Elissa K Ma, Yuanqing Phan, Tri Lim, Elgene Joshua, Anthony M Walters, Stacey Grey, Shane T Shi, Yan-Chuan Zhang, Lei Herzog, Herbert Croucher, David R Philp, Andy Scheele, Colinda L G J Herrmann, David Sansom, Owen J Morton, Jennifer P Papa, Antonella Haigh, Jody J Nobis, Max Timpson, Paul |
| description | Aberrant AKT activation occurs in a number of cancers, metabolic syndrome, and immune disorders, making it an important target for the treatment of many diseases. To monitor spatial and temporal AKT activity in a live setting, we generated an Akt-FRET biosensor mouse that allows longitudinal assessment of AKT activity using intravital imaging in conjunction with image stabilization and optical window technology. We demonstrate the sensitivity of the Akt-FRET biosensor mouse using various cancer models and verify its suitability to monitor response to drug targeting in spheroid and organotypic models. We also show that the dynamics of AKT activation can be monitored in real time in diverse tissues, including in individual islets of the pancreas, in the brown and white adipose tissue, and in the skeletal muscle. Thus, the Akt-FRET biosensor mouse provides an important tool to study AKT dynamics in live tissue contexts and has broad preclinical applications. |
| doi_str_mv | 10.1126/sciadv.adf9063 |
| format | Article |
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To monitor spatial and temporal AKT activity in a live setting, we generated an Akt-FRET biosensor mouse that allows longitudinal assessment of AKT activity using intravital imaging in conjunction with image stabilization and optical window technology. We demonstrate the sensitivity of the Akt-FRET biosensor mouse using various cancer models and verify its suitability to monitor response to drug targeting in spheroid and organotypic models. We also show that the dynamics of AKT activation can be monitored in real time in diverse tissues, including in individual islets of the pancreas, in the brown and white adipose tissue, and in the skeletal muscle. Thus, the Akt-FRET biosensor mouse provides an important tool to study AKT dynamics in live tissue contexts and has broad preclinical applications.</description><identifier>ISSN: 2375-2548</identifier><identifier>EISSN: 2375-2548</identifier><identifier>DOI: 10.1126/sciadv.adf9063</identifier><identifier>PMID: 37126544</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Animals ; Biomedicine and Life Sciences ; Biosensing Techniques - methods ; Cancer ; Fluorescence Resonance Energy Transfer - methods ; Mice ; Proto-Oncogene Proteins c-akt - metabolism ; Research Resource ; SciAdv r-resources ; Signal Transduction</subject><ispartof>Science advances, 2023-04, Vol.9 (17), p.eadf9063</ispartof><rights>Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). 2023 The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c391t-4db3542dd432dadc6cb18ebca38c2fba80602f4406f2a6cbe148d1390792aef23</citedby><cites>FETCH-LOGICAL-c391t-4db3542dd432dadc6cb18ebca38c2fba80602f4406f2a6cbe148d1390792aef23</cites><orcidid>0000-0002-0701-8321 ; 0000-0002-7319-8922 ; 0000-0001-5159-4580 ; 0000-0002-8368-6735 ; 0000-0003-2160-1625 ; 0000-0001-8999-5451 ; 0000-0001-9599-9280 ; 0000-0003-4965-8674 ; 0000-0002-9514-7501 ; 0000-0002-4198-3520 ; 0000-0002-5253-7147 ; 0000-0002-9271-0004 ; 0000-0001-5766-9141 ; 0000-0001-8065-8838 ; 0000-0002-3736-7725 ; 0000-0002-3234-3812 ; 0000-0002-1861-1390 ; 0000-0001-5937-2341 ; 0000-0001-6486-2003 ; 0000-0003-2676-2575 ; 0000-0002-5514-7080 ; 0000-0003-3787-277X ; 0000-0003-1128-5315 ; 0000-0001-8653-7121 ; 0000-0002-3927-8881 ; 0000-0003-0212-0164 ; 0000-0001-9540-3010 ; 0000-0003-0557-4559 ; 0000-0002-4979-9349 ; 0000-0003-3513-1214 ; 0000-0002-4909-2984</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10132756/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10132756/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37126544$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Conway, James R W</creatorcontrib><creatorcontrib>Warren, Sean C</creatorcontrib><creatorcontrib>Lee, Young-Kyung</creatorcontrib><creatorcontrib>McCulloch, Andrew T</creatorcontrib><creatorcontrib>Magenau, Astrid</creatorcontrib><creatorcontrib>Lee, Victoria</creatorcontrib><creatorcontrib>Metcalf, Xanthe L</creatorcontrib><creatorcontrib>Stoehr, Janett</creatorcontrib><creatorcontrib>Haigh, Katharina</creatorcontrib><creatorcontrib>Abdulkhalek, Lea</creatorcontrib><creatorcontrib>Guaman, Cristian S</creatorcontrib><creatorcontrib>Reed, Daniel A</creatorcontrib><creatorcontrib>Murphy, Kendelle J</creatorcontrib><creatorcontrib>Pereira, Brooke A</creatorcontrib><creatorcontrib>Mélénec, Pauline</creatorcontrib><creatorcontrib>Chambers, Cecilia</creatorcontrib><creatorcontrib>Latham, Sharissa L</creatorcontrib><creatorcontrib>Lenthall, Helen</creatorcontrib><creatorcontrib>Deenick, Elissa K</creatorcontrib><creatorcontrib>Ma, Yuanqing</creatorcontrib><creatorcontrib>Phan, Tri</creatorcontrib><creatorcontrib>Lim, Elgene</creatorcontrib><creatorcontrib>Joshua, Anthony M</creatorcontrib><creatorcontrib>Walters, Stacey</creatorcontrib><creatorcontrib>Grey, Shane T</creatorcontrib><creatorcontrib>Shi, Yan-Chuan</creatorcontrib><creatorcontrib>Zhang, Lei</creatorcontrib><creatorcontrib>Herzog, Herbert</creatorcontrib><creatorcontrib>Croucher, David R</creatorcontrib><creatorcontrib>Philp, Andy</creatorcontrib><creatorcontrib>Scheele, Colinda L G J</creatorcontrib><creatorcontrib>Herrmann, David</creatorcontrib><creatorcontrib>Sansom, Owen J</creatorcontrib><creatorcontrib>Morton, Jennifer P</creatorcontrib><creatorcontrib>Papa, Antonella</creatorcontrib><creatorcontrib>Haigh, Jody J</creatorcontrib><creatorcontrib>Nobis, Max</creatorcontrib><creatorcontrib>Timpson, Paul</creatorcontrib><title>Monitoring AKT activity and targeting in live tissue and disease contexts using a real-time Akt-FRET biosensor mouse</title><title>Science advances</title><addtitle>Sci Adv</addtitle><description>Aberrant AKT activation occurs in a number of cancers, metabolic syndrome, and immune disorders, making it an important target for the treatment of many diseases. 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Thus, the Akt-FRET biosensor mouse provides an important tool to study AKT dynamics in live tissue contexts and has broad preclinical applications.</description><subject>Animals</subject><subject>Biomedicine and Life Sciences</subject><subject>Biosensing Techniques - methods</subject><subject>Cancer</subject><subject>Fluorescence Resonance Energy Transfer - methods</subject><subject>Mice</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Research Resource</subject><subject>SciAdv r-resources</subject><subject>Signal 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advances</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Conway, James R W</au><au>Warren, Sean C</au><au>Lee, Young-Kyung</au><au>McCulloch, Andrew T</au><au>Magenau, Astrid</au><au>Lee, Victoria</au><au>Metcalf, Xanthe L</au><au>Stoehr, Janett</au><au>Haigh, Katharina</au><au>Abdulkhalek, Lea</au><au>Guaman, Cristian S</au><au>Reed, Daniel A</au><au>Murphy, Kendelle J</au><au>Pereira, Brooke A</au><au>Mélénec, Pauline</au><au>Chambers, Cecilia</au><au>Latham, Sharissa L</au><au>Lenthall, Helen</au><au>Deenick, Elissa K</au><au>Ma, Yuanqing</au><au>Phan, Tri</au><au>Lim, Elgene</au><au>Joshua, Anthony M</au><au>Walters, Stacey</au><au>Grey, Shane T</au><au>Shi, Yan-Chuan</au><au>Zhang, Lei</au><au>Herzog, Herbert</au><au>Croucher, David R</au><au>Philp, Andy</au><au>Scheele, Colinda L G J</au><au>Herrmann, David</au><au>Sansom, Owen J</au><au>Morton, Jennifer P</au><au>Papa, Antonella</au><au>Haigh, Jody J</au><au>Nobis, Max</au><au>Timpson, Paul</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Monitoring AKT activity and targeting in live tissue and disease contexts using a real-time Akt-FRET biosensor mouse</atitle><jtitle>Science advances</jtitle><addtitle>Sci Adv</addtitle><date>2023-04-28</date><risdate>2023</risdate><volume>9</volume><issue>17</issue><spage>eadf9063</spage><pages>eadf9063-</pages><issn>2375-2548</issn><eissn>2375-2548</eissn><abstract>Aberrant AKT activation occurs in a number of cancers, metabolic syndrome, and immune disorders, making it an important target for the treatment of many diseases. To monitor spatial and temporal AKT activity in a live setting, we generated an Akt-FRET biosensor mouse that allows longitudinal assessment of AKT activity using intravital imaging in conjunction with image stabilization and optical window technology. We demonstrate the sensitivity of the Akt-FRET biosensor mouse using various cancer models and verify its suitability to monitor response to drug targeting in spheroid and organotypic models. We also show that the dynamics of AKT activation can be monitored in real time in diverse tissues, including in individual islets of the pancreas, in the brown and white adipose tissue, and in the skeletal muscle. Thus, the Akt-FRET biosensor mouse provides an important tool to study AKT dynamics in live tissue contexts and has broad preclinical applications.</abstract><cop>United States</cop><pub>American Association for the Advancement of Science</pub><pmid>37126544</pmid><doi>10.1126/sciadv.adf9063</doi><orcidid>https://orcid.org/0000-0002-0701-8321</orcidid><orcidid>https://orcid.org/0000-0002-7319-8922</orcidid><orcidid>https://orcid.org/0000-0001-5159-4580</orcidid><orcidid>https://orcid.org/0000-0002-8368-6735</orcidid><orcidid>https://orcid.org/0000-0003-2160-1625</orcidid><orcidid>https://orcid.org/0000-0001-8999-5451</orcidid><orcidid>https://orcid.org/0000-0001-9599-9280</orcidid><orcidid>https://orcid.org/0000-0003-4965-8674</orcidid><orcidid>https://orcid.org/0000-0002-9514-7501</orcidid><orcidid>https://orcid.org/0000-0002-4198-3520</orcidid><orcidid>https://orcid.org/0000-0002-5253-7147</orcidid><orcidid>https://orcid.org/0000-0002-9271-0004</orcidid><orcidid>https://orcid.org/0000-0001-5766-9141</orcidid><orcidid>https://orcid.org/0000-0001-8065-8838</orcidid><orcidid>https://orcid.org/0000-0002-3736-7725</orcidid><orcidid>https://orcid.org/0000-0002-3234-3812</orcidid><orcidid>https://orcid.org/0000-0002-1861-1390</orcidid><orcidid>https://orcid.org/0000-0001-5937-2341</orcidid><orcidid>https://orcid.org/0000-0001-6486-2003</orcidid><orcidid>https://orcid.org/0000-0003-2676-2575</orcidid><orcidid>https://orcid.org/0000-0002-5514-7080</orcidid><orcidid>https://orcid.org/0000-0003-3787-277X</orcidid><orcidid>https://orcid.org/0000-0003-1128-5315</orcidid><orcidid>https://orcid.org/0000-0001-8653-7121</orcidid><orcidid>https://orcid.org/0000-0002-3927-8881</orcidid><orcidid>https://orcid.org/0000-0003-0212-0164</orcidid><orcidid>https://orcid.org/0000-0001-9540-3010</orcidid><orcidid>https://orcid.org/0000-0003-0557-4559</orcidid><orcidid>https://orcid.org/0000-0002-4979-9349</orcidid><orcidid>https://orcid.org/0000-0003-3513-1214</orcidid><orcidid>https://orcid.org/0000-0002-4909-2984</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2375-2548 |
| ispartof | Science advances, 2023-04, Vol.9 (17), p.eadf9063 |
| issn | 2375-2548 2375-2548 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10132756 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Animals Biomedicine and Life Sciences Biosensing Techniques - methods Cancer Fluorescence Resonance Energy Transfer - methods Mice Proto-Oncogene Proteins c-akt - metabolism Research Resource SciAdv r-resources Signal Transduction |
| title | Monitoring AKT activity and targeting in live tissue and disease contexts using a real-time Akt-FRET biosensor mouse |
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