Behavioral characterization of a CRISPR-generated TRPA1 knockout rat in models of pain, itch, and asthma
Identifieur interne : 000201 ( Pmc/Curation ); précédent : 000200; suivant : 000202Behavioral characterization of a CRISPR-generated TRPA1 knockout rat in models of pain, itch, and asthma
Auteurs : Rebecca M. Reese [États-Unis] ; Michelle Dourado [États-Unis] ; Keith Anderson [États-Unis] ; S Ren Warming [États-Unis] ; Kimberly L. Stark [États-Unis] ; Alessia Balestrini [États-Unis] ; Eric Suto [États-Unis] ; Wyne Lee [États-Unis] ; Lorena Riol-Blanco [États-Unis] ; Shannon D. Shields [États-Unis] ; David H. Hackos [États-Unis]Source :
- Scientific Reports [ 2045-2322 ] ; 2020.
Abstract
The transient receptor potential (TRP) superfamily of ion channels has garnered significant attention by the pharmaceutical industry. In particular, TRP channels showing high levels of expression in sensory neurons such as TRPV1, TRPA1, and TRPM8, have been considered as targets for indications where sensory neurons play a fundamental role, such as pain, itch, and asthma. Modeling these indications in rodents is challenging, especially in mice. The rat is the preferred species for pharmacological studies in pain, itch, and asthma, but until recently, genetic manipulation of the rat has been technically challenging. Here, using CRISPR technology, we have generated a TRPA1 KO rat to enable more sophisticated modeling of pain, itch, and asthma. We present a detailed phenotyping of the TRPA1 KO rat in models of pain, itch, and asthma that have previously only been investigated in the mouse. With the exception of nociception induced by direct TRPA1 activation, we have found that the TRPA1 KO rat shows apparently normal behavioral responses in multiple models of pain and itch. Immune cell infiltration into the lung in the rat OVA model of asthma, on the other hand, appears to be dependent on TRPA1, similar to was has been observed in TRPA1 KO mice. Our hope is that the TRPA1 KO rat will become a useful tool in further studies of TRPA1 as a drug target.
Url:
DOI: 10.1038/s41598-020-57936-5
PubMed: 31969645
PubMed Central: 6976688
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: Pour aller vers cette notice dans l'étape Curation :000201
Links to Exploration step
PMC:6976688Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Behavioral characterization of a CRISPR-generated TRPA1 knockout rat in models of pain, itch, and asthma</title>
<author><name sortKey="Reese, Rebecca M" sort="Reese, Rebecca M" uniqKey="Reese R" first="Rebecca M." last="Reese">Rebecca M. Reese</name>
<affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0534 4718</institution-id>
<institution-id institution-id-type="GRID">grid.418158.1</institution-id>
<institution>Department of Neuroscience,</institution>
<institution>Genentech, 1 DNA Way,</institution>
</institution-wrap>
South San Francisco, CA 94080 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>South San Francisco</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Dourado, Michelle" sort="Dourado, Michelle" uniqKey="Dourado M" first="Michelle" last="Dourado">Michelle Dourado</name>
<affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0534 4718</institution-id>
<institution-id institution-id-type="GRID">grid.418158.1</institution-id>
<institution>Department of Neuroscience,</institution>
<institution>Genentech, 1 DNA Way,</institution>
</institution-wrap>
South San Francisco, CA 94080 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>South San Francisco</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Anderson, Keith" sort="Anderson, Keith" uniqKey="Anderson K" first="Keith" last="Anderson">Keith Anderson</name>
<affiliation wicri:level="2"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0534 4718</institution-id>
<institution-id institution-id-type="GRID">grid.418158.1</institution-id>
<institution>Department of Molecular Biology,</institution>
<institution>Genentech, 1 DNA Way,</institution>
</institution-wrap>
South San Francisco, CA 94080 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>South San Francisco</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Warming, S Ren" sort="Warming, S Ren" uniqKey="Warming S" first="S Ren" last="Warming">S Ren Warming</name>
<affiliation wicri:level="2"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0534 4718</institution-id>
<institution-id institution-id-type="GRID">grid.418158.1</institution-id>
<institution>Department of Molecular Biology,</institution>
<institution>Genentech, 1 DNA Way,</institution>
</institution-wrap>
South San Francisco, CA 94080 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>South San Francisco</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Stark, Kimberly L" sort="Stark, Kimberly L" uniqKey="Stark K" first="Kimberly L." last="Stark">Kimberly L. Stark</name>
<affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0534 4718</institution-id>
<institution-id institution-id-type="GRID">grid.418158.1</institution-id>
<institution>Department of Neuroscience,</institution>
<institution>Genentech, 1 DNA Way,</institution>
</institution-wrap>
South San Francisco, CA 94080 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>South San Francisco</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Balestrini, Alessia" sort="Balestrini, Alessia" uniqKey="Balestrini A" first="Alessia" last="Balestrini">Alessia Balestrini</name>
<affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0534 4718</institution-id>
<institution-id institution-id-type="GRID">grid.418158.1</institution-id>
<institution>Department of Immunology,</institution>
<institution>Genentech, 1 DNA Way,</institution>
</institution-wrap>
South San Francisco, CA 94080 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>South San Francisco</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Suto, Eric" sort="Suto, Eric" uniqKey="Suto E" first="Eric" last="Suto">Eric Suto</name>
<affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0534 4718</institution-id>
<institution-id institution-id-type="GRID">grid.418158.1</institution-id>
<institution>Department of Immunology,</institution>
<institution>Genentech, 1 DNA Way,</institution>
</institution-wrap>
South San Francisco, CA 94080 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>South San Francisco</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Lee, Wyne" sort="Lee, Wyne" uniqKey="Lee W" first="Wyne" last="Lee">Wyne Lee</name>
<affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0534 4718</institution-id>
<institution-id institution-id-type="GRID">grid.418158.1</institution-id>
<institution>Department of Immunology,</institution>
<institution>Genentech, 1 DNA Way,</institution>
</institution-wrap>
South San Francisco, CA 94080 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>South San Francisco</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Riol Blanco, Lorena" sort="Riol Blanco, Lorena" uniqKey="Riol Blanco L" first="Lorena" last="Riol-Blanco">Lorena Riol-Blanco</name>
<affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0534 4718</institution-id>
<institution-id institution-id-type="GRID">grid.418158.1</institution-id>
<institution>Department of Immunology,</institution>
<institution>Genentech, 1 DNA Way,</institution>
</institution-wrap>
South San Francisco, CA 94080 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>South San Francisco</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Shields, Shannon D" sort="Shields, Shannon D" uniqKey="Shields S" first="Shannon D." last="Shields">Shannon D. Shields</name>
<affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0534 4718</institution-id>
<institution-id institution-id-type="GRID">grid.418158.1</institution-id>
<institution>Department of Neuroscience,</institution>
<institution>Genentech, 1 DNA Way,</institution>
</institution-wrap>
South San Francisco, CA 94080 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>South San Francisco</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Hackos, David H" sort="Hackos, David H" uniqKey="Hackos D" first="David H." last="Hackos">David H. Hackos</name>
<affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0534 4718</institution-id>
<institution-id institution-id-type="GRID">grid.418158.1</institution-id>
<institution>Department of Neuroscience,</institution>
<institution>Genentech, 1 DNA Way,</institution>
</institution-wrap>
South San Francisco, CA 94080 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>South San Francisco</wicri:cityArea>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">31969645</idno>
<idno type="pmc">6976688</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976688</idno>
<idno type="RBID">PMC:6976688</idno>
<idno type="doi">10.1038/s41598-020-57936-5</idno>
<date when="2020">2020</date>
<idno type="wicri:Area/Pmc/Corpus">000201</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000201</idno>
<idno type="wicri:Area/Pmc/Curation">000201</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000201</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Behavioral characterization of a CRISPR-generated TRPA1 knockout rat in models of pain, itch, and asthma</title>
<author><name sortKey="Reese, Rebecca M" sort="Reese, Rebecca M" uniqKey="Reese R" first="Rebecca M." last="Reese">Rebecca M. Reese</name>
<affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0534 4718</institution-id>
<institution-id institution-id-type="GRID">grid.418158.1</institution-id>
<institution>Department of Neuroscience,</institution>
<institution>Genentech, 1 DNA Way,</institution>
</institution-wrap>
South San Francisco, CA 94080 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>South San Francisco</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Dourado, Michelle" sort="Dourado, Michelle" uniqKey="Dourado M" first="Michelle" last="Dourado">Michelle Dourado</name>
<affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0534 4718</institution-id>
<institution-id institution-id-type="GRID">grid.418158.1</institution-id>
<institution>Department of Neuroscience,</institution>
<institution>Genentech, 1 DNA Way,</institution>
</institution-wrap>
South San Francisco, CA 94080 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>South San Francisco</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Anderson, Keith" sort="Anderson, Keith" uniqKey="Anderson K" first="Keith" last="Anderson">Keith Anderson</name>
<affiliation wicri:level="2"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0534 4718</institution-id>
<institution-id institution-id-type="GRID">grid.418158.1</institution-id>
<institution>Department of Molecular Biology,</institution>
<institution>Genentech, 1 DNA Way,</institution>
</institution-wrap>
South San Francisco, CA 94080 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>South San Francisco</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Warming, S Ren" sort="Warming, S Ren" uniqKey="Warming S" first="S Ren" last="Warming">S Ren Warming</name>
<affiliation wicri:level="2"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0534 4718</institution-id>
<institution-id institution-id-type="GRID">grid.418158.1</institution-id>
<institution>Department of Molecular Biology,</institution>
<institution>Genentech, 1 DNA Way,</institution>
</institution-wrap>
South San Francisco, CA 94080 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>South San Francisco</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Stark, Kimberly L" sort="Stark, Kimberly L" uniqKey="Stark K" first="Kimberly L." last="Stark">Kimberly L. Stark</name>
<affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0534 4718</institution-id>
<institution-id institution-id-type="GRID">grid.418158.1</institution-id>
<institution>Department of Neuroscience,</institution>
<institution>Genentech, 1 DNA Way,</institution>
</institution-wrap>
South San Francisco, CA 94080 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>South San Francisco</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Balestrini, Alessia" sort="Balestrini, Alessia" uniqKey="Balestrini A" first="Alessia" last="Balestrini">Alessia Balestrini</name>
<affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0534 4718</institution-id>
<institution-id institution-id-type="GRID">grid.418158.1</institution-id>
<institution>Department of Immunology,</institution>
<institution>Genentech, 1 DNA Way,</institution>
</institution-wrap>
South San Francisco, CA 94080 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>South San Francisco</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Suto, Eric" sort="Suto, Eric" uniqKey="Suto E" first="Eric" last="Suto">Eric Suto</name>
<affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0534 4718</institution-id>
<institution-id institution-id-type="GRID">grid.418158.1</institution-id>
<institution>Department of Immunology,</institution>
<institution>Genentech, 1 DNA Way,</institution>
</institution-wrap>
South San Francisco, CA 94080 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>South San Francisco</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Lee, Wyne" sort="Lee, Wyne" uniqKey="Lee W" first="Wyne" last="Lee">Wyne Lee</name>
<affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0534 4718</institution-id>
<institution-id institution-id-type="GRID">grid.418158.1</institution-id>
<institution>Department of Immunology,</institution>
<institution>Genentech, 1 DNA Way,</institution>
</institution-wrap>
South San Francisco, CA 94080 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>South San Francisco</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Riol Blanco, Lorena" sort="Riol Blanco, Lorena" uniqKey="Riol Blanco L" first="Lorena" last="Riol-Blanco">Lorena Riol-Blanco</name>
<affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0534 4718</institution-id>
<institution-id institution-id-type="GRID">grid.418158.1</institution-id>
<institution>Department of Immunology,</institution>
<institution>Genentech, 1 DNA Way,</institution>
</institution-wrap>
South San Francisco, CA 94080 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>South San Francisco</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Shields, Shannon D" sort="Shields, Shannon D" uniqKey="Shields S" first="Shannon D." last="Shields">Shannon D. Shields</name>
<affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0534 4718</institution-id>
<institution-id institution-id-type="GRID">grid.418158.1</institution-id>
<institution>Department of Neuroscience,</institution>
<institution>Genentech, 1 DNA Way,</institution>
</institution-wrap>
South San Francisco, CA 94080 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>South San Francisco</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Hackos, David H" sort="Hackos, David H" uniqKey="Hackos D" first="David H." last="Hackos">David H. Hackos</name>
<affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0534 4718</institution-id>
<institution-id institution-id-type="GRID">grid.418158.1</institution-id>
<institution>Department of Neuroscience,</institution>
<institution>Genentech, 1 DNA Way,</institution>
</institution-wrap>
South San Francisco, CA 94080 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>South San Francisco</wicri:cityArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Scientific Reports</title>
<idno type="eISSN">2045-2322</idno>
<imprint><date when="2020">2020</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p id="Par1">The transient receptor potential (TRP) superfamily of ion channels has garnered significant attention by the pharmaceutical industry. In particular, TRP channels showing high levels of expression in sensory neurons such as TRPV1, TRPA1, and TRPM8, have been considered as targets for indications where sensory neurons play a fundamental role, such as pain, itch, and asthma. Modeling these indications in rodents is challenging, especially in mice. The rat is the preferred species for pharmacological studies in pain, itch, and asthma, but until recently, genetic manipulation of the rat has been technically challenging. Here, using CRISPR technology, we have generated a TRPA1 KO rat to enable more sophisticated modeling of pain, itch, and asthma. We present a detailed phenotyping of the TRPA1 KO rat in models of pain, itch, and asthma that have previously only been investigated in the mouse. With the exception of nociception induced by direct TRPA1 activation, we have found that the TRPA1 KO rat shows apparently normal behavioral responses in multiple models of pain and itch. Immune cell infiltration into the lung in the rat OVA model of asthma, on the other hand, appears to be dependent on TRPA1, similar to was has been observed in TRPA1 KO mice. Our hope is that the TRPA1 KO rat will become a useful tool in further studies of TRPA1 as a drug target.</p>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Nagata, K" uniqKey="Nagata K">K Nagata</name>
</author>
<author><name sortKey="Duggan, A" uniqKey="Duggan A">A Duggan</name>
</author>
<author><name sortKey="Kumar, G" uniqKey="Kumar G">G Kumar</name>
</author>
<author><name sortKey="Garcia A Overos, J" uniqKey="Garcia A Overos J">J García-Añoveros</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Story, Gm" uniqKey="Story G">GM Story</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bandell, M" uniqKey="Bandell M">M Bandell</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bautista, Dm" uniqKey="Bautista D">DM Bautista</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bessac, Bf" uniqKey="Bessac B">BF Bessac</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jordt, S E" uniqKey="Jordt S">S-E Jordt</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Macpherson, Lj" uniqKey="Macpherson L">LJ Macpherson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chen, J" uniqKey="Chen J">J Chen</name>
</author>
<author><name sortKey="Hackos, Dh" uniqKey="Hackos D">DH Hackos</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bautista, Dm" uniqKey="Bautista D">DM Bautista</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Caceres, Ai" uniqKey="Caceres A">AI Caceres</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kwan, Ky" uniqKey="Kwan K">KY Kwan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Morita, T" uniqKey="Morita T">T Morita</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Nassini, R" uniqKey="Nassini R">R Nassini</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Trevisan, G" uniqKey="Trevisan G">G Trevisan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wilson, Sr" uniqKey="Wilson S">SR Wilson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Barabas, Me" uniqKey="Barabas M">ME Barabas</name>
</author>
<author><name sortKey="Kossyreva, Ea" uniqKey="Kossyreva E">EA Kossyreva</name>
</author>
<author><name sortKey="Stucky, Cl" uniqKey="Stucky C">CL Stucky</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Obata, K" uniqKey="Obata K">K Obata</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Niforatos, W" uniqKey="Niforatos W">W Niforatos</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Brenner, Ds" uniqKey="Brenner D">DS Brenner</name>
</author>
<author><name sortKey="Golden, Jp" uniqKey="Golden J">JP Golden</name>
</author>
<author><name sortKey="Gereau, Rw" uniqKey="Gereau R">RW Gereau</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cho, J H" uniqKey="Cho J">J-H Cho</name>
</author>
<author><name sortKey="Jeong, M Y" uniqKey="Jeong M">M-Y Jeong</name>
</author>
<author><name sortKey="Choi, I S" uniqKey="Choi I">I-S Choi</name>
</author>
<author><name sortKey="Lee, H J" uniqKey="Lee H">H-J Lee</name>
</author>
<author><name sortKey="Jang, I S" uniqKey="Jang I">I-S Jang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Fajardo, O" uniqKey="Fajardo O">O Fajardo</name>
</author>
<author><name sortKey="Meseguer, V" uniqKey="Meseguer V">V Meseguer</name>
</author>
<author><name sortKey="Belmonte, C" uniqKey="Belmonte C">C Belmonte</name>
</author>
<author><name sortKey="Viana, F" uniqKey="Viana F">F Viana</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="De Petrocellis, L" uniqKey="De Petrocellis L">L De Petrocellis</name>
</author>
<author><name sortKey="Ortar, G" uniqKey="Ortar G">G Ortar</name>
</author>
<author><name sortKey="Schiano Moriello, A" uniqKey="Schiano Moriello A">A Schiano Moriello</name>
</author>
<author><name sortKey="Serum, Em" uniqKey="Serum E">EM Serum</name>
</author>
<author><name sortKey="Rusterholz, Db" uniqKey="Rusterholz D">DB Rusterholz</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Ohmi, M" uniqKey="Ohmi M">M Ohmi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Werkheiser, Jl" uniqKey="Werkheiser J">JL Werkheiser</name>
</author>
<author><name sortKey="Rawls, Sm" uniqKey="Rawls S">SM Rawls</name>
</author>
<author><name sortKey="Cowan, A" uniqKey="Cowan A">A Cowan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Knowlton, Wm" uniqKey="Knowlton W">WM Knowlton</name>
</author>
<author><name sortKey="Bifolck Fisher, A" uniqKey="Bifolck Fisher A">A Bifolck-Fisher</name>
</author>
<author><name sortKey="Bautista, Dm" uniqKey="Bautista D">DM Bautista</name>
</author>
<author><name sortKey="Mckemy, Dd" uniqKey="Mckemy D">DD McKemy</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Old, Ea" uniqKey="Old E">EA Old</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Huang, Q" uniqKey="Huang Q">Q Huang</name>
</author>
<author><name sortKey="Chen, Y" uniqKey="Chen Y">Y Chen</name>
</author>
<author><name sortKey="Gong, N" uniqKey="Gong N">N Gong</name>
</author>
<author><name sortKey="Wang, Y X" uniqKey="Wang Y">Y-X Wang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bennett, Gj" uniqKey="Bennett G">GJ Bennett</name>
</author>
<author><name sortKey="Xie, Yk" uniqKey="Xie Y">YK Xie</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Eid, Sr" uniqKey="Eid S">SR Eid</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lennertz, Rc" uniqKey="Lennertz R">RC Lennertz</name>
</author>
<author><name sortKey="Kossyreva, Ea" uniqKey="Kossyreva E">EA Kossyreva</name>
</author>
<author><name sortKey="Smith, Ak" uniqKey="Smith A">AK Smith</name>
</author>
<author><name sortKey="Stucky, Cl" uniqKey="Stucky C">CL Stucky</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Asgar, J" uniqKey="Asgar J">J Asgar</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Petrus, M" uniqKey="Petrus M">M Petrus</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Wilson, Sr" uniqKey="Wilson S">SR Wilson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ru, F" uniqKey="Ru F">F Ru</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chen, J" uniqKey="Chen J">J Chen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Akopian, An" uniqKey="Akopian A">AN Akopian</name>
</author>
<author><name sortKey="Ruparel, Nb" uniqKey="Ruparel N">NB Ruparel</name>
</author>
<author><name sortKey="Jeske, Na" uniqKey="Jeske N">NA Jeske</name>
</author>
<author><name sortKey="Hargreaves, Km" uniqKey="Hargreaves K">KM Hargreaves</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Fischer, Mjm" uniqKey="Fischer M">MJM Fischer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Salas, Mm" uniqKey="Salas M">MM Salas</name>
</author>
<author><name sortKey="Hargreaves, Km" uniqKey="Hargreaves K">KM Hargreaves</name>
</author>
<author><name sortKey="Akopian, An" uniqKey="Akopian A">AN Akopian</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Spahn, V" uniqKey="Spahn V">V Spahn</name>
</author>
<author><name sortKey="Stein, C" uniqKey="Stein C">C Stein</name>
</author>
<author><name sortKey="Zollner, C" uniqKey="Zollner C">C Zöllner</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Staruschenko, A" uniqKey="Staruschenko A">A Staruschenko</name>
</author>
<author><name sortKey="Jeske, Na" uniqKey="Jeske N">NA Jeske</name>
</author>
<author><name sortKey="Akopian, An" uniqKey="Akopian A">AN Akopian</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Weng, H J" uniqKey="Weng H">H-J Weng</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chaplan, Sr" uniqKey="Chaplan S">SR Chaplan</name>
</author>
<author><name sortKey="Bach, Fw" uniqKey="Bach F">FW Bach</name>
</author>
<author><name sortKey="Pogrel, Jw" uniqKey="Pogrel J">JW Pogrel</name>
</author>
<author><name sortKey="Chung, Jm" uniqKey="Chung J">JM Chung</name>
</author>
<author><name sortKey="Yaksh, Tl" uniqKey="Yaksh T">TL Yaksh</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Sci Rep</journal-id>
<journal-id journal-id-type="iso-abbrev">Sci Rep</journal-id>
<journal-title-group><journal-title>Scientific Reports</journal-title>
</journal-title-group>
<issn pub-type="epub">2045-2322</issn>
<publisher><publisher-name>Nature Publishing Group UK</publisher-name>
<publisher-loc>London</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">31969645</article-id>
<article-id pub-id-type="pmc">6976688</article-id>
<article-id pub-id-type="publisher-id">57936</article-id>
<article-id pub-id-type="doi">10.1038/s41598-020-57936-5</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Behavioral characterization of a CRISPR-generated TRPA1 knockout rat in models of pain, itch, and asthma</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Reese</surname>
<given-names>Rebecca M.</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Dourado</surname>
<given-names>Michelle</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0001-8713-4965</contrib-id>
<name><surname>Anderson</surname>
<given-names>Keith</given-names>
</name>
<xref ref-type="aff" rid="Aff3">3</xref>
</contrib>
<contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-5721-0741</contrib-id>
<name><surname>Warming</surname>
<given-names>Søren</given-names>
</name>
<xref ref-type="aff" rid="Aff3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Stark</surname>
<given-names>Kimberly L.</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Balestrini</surname>
<given-names>Alessia</given-names>
</name>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Suto</surname>
<given-names>Eric</given-names>
</name>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lee</surname>
<given-names>Wyne</given-names>
</name>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Riol-Blanco</surname>
<given-names>Lorena</given-names>
</name>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Shields</surname>
<given-names>Shannon D.</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Hackos</surname>
<given-names>David H.</given-names>
</name>
<address><email>hackos.david@gene.com</email>
</address>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<aff id="Aff1"><label>1</label>
<institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0534 4718</institution-id>
<institution-id institution-id-type="GRID">grid.418158.1</institution-id>
<institution>Department of Neuroscience,</institution>
<institution>Genentech, 1 DNA Way,</institution>
</institution-wrap>
South San Francisco, CA 94080 USA</aff>
<aff id="Aff2"><label>2</label>
<institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0534 4718</institution-id>
<institution-id institution-id-type="GRID">grid.418158.1</institution-id>
<institution>Department of Immunology,</institution>
<institution>Genentech, 1 DNA Way,</institution>
</institution-wrap>
South San Francisco, CA 94080 USA</aff>
<aff id="Aff3"><label>3</label>
<institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0534 4718</institution-id>
<institution-id institution-id-type="GRID">grid.418158.1</institution-id>
<institution>Department of Molecular Biology,</institution>
<institution>Genentech, 1 DNA Way,</institution>
</institution-wrap>
South San Francisco, CA 94080 USA</aff>
</contrib-group>
<pub-date pub-type="epub"><day>22</day>
<month>1</month>
<year>2020</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>22</day>
<month>1</month>
<year>2020</year>
</pub-date>
<pub-date pub-type="collection"><year>2020</year>
</pub-date>
<volume>10</volume>
<elocation-id>979</elocation-id>
<history><date date-type="received"><day>25</day>
<month>9</month>
<year>2019</year>
</date>
<date date-type="accepted"><day>3</day>
<month>1</month>
<year>2020</year>
</date>
</history>
<permissions><copyright-statement>© The Author(s) 2020</copyright-statement>
<license license-type="OpenAccess"><license-p><bold>Open Access</bold>
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
.</license-p>
</license>
</permissions>
<abstract id="Abs1"><p id="Par1">The transient receptor potential (TRP) superfamily of ion channels has garnered significant attention by the pharmaceutical industry. In particular, TRP channels showing high levels of expression in sensory neurons such as TRPV1, TRPA1, and TRPM8, have been considered as targets for indications where sensory neurons play a fundamental role, such as pain, itch, and asthma. Modeling these indications in rodents is challenging, especially in mice. The rat is the preferred species for pharmacological studies in pain, itch, and asthma, but until recently, genetic manipulation of the rat has been technically challenging. Here, using CRISPR technology, we have generated a TRPA1 KO rat to enable more sophisticated modeling of pain, itch, and asthma. We present a detailed phenotyping of the TRPA1 KO rat in models of pain, itch, and asthma that have previously only been investigated in the mouse. With the exception of nociception induced by direct TRPA1 activation, we have found that the TRPA1 KO rat shows apparently normal behavioral responses in multiple models of pain and itch. Immune cell infiltration into the lung in the rat OVA model of asthma, on the other hand, appears to be dependent on TRPA1, similar to was has been observed in TRPA1 KO mice. Our hope is that the TRPA1 KO rat will become a useful tool in further studies of TRPA1 as a drug target.</p>
</abstract>
<kwd-group kwd-group-type="npg-subject"><title>Subject terms</title>
<kwd>Ion channels in the nervous system</kwd>
<kwd>Chronic pain</kwd>
</kwd-group>
<custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name>
<meta-value>© The Author(s) 2020</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/ChloroquineV1/Data/Pmc/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000201 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd -nk 000201 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= ChloroquineV1 |flux= Pmc |étape= Curation |type= RBID |clé= PMC:6976688 |texte= Behavioral characterization of a CRISPR-generated TRPA1 knockout rat in models of pain, itch, and asthma }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Curation/RBID.i -Sk "pubmed:31969645" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd \ | NlmPubMed2Wicri -a ChloroquineV1
This area was generated with Dilib version V0.6.33. |