Essential Role of the Coxsackie - and Adenovirus Receptor (CAR) in Development of the Lymphatic System in Mice
Identifieur interne : 004331 ( Main/Exploration ); précédent : 004330; suivant : 004332Essential Role of the Coxsackie - and Adenovirus Receptor (CAR) in Development of the Lymphatic System in Mice
Auteurs : Momina Mirza [Suède] ; Mei-Fong Pang [Suède] ; Mohamad Amr Zaini [Suède] ; Paula Haiko [Finlande] ; Tuomas Tammela [Finlande] ; Kari Alitalo [Finlande] ; Lennart Philipson [Suède] ; Jonas Fuxe [Suède] ; Kerstin Sollerbrant [Suède]Source :
- PLoS ONE [ 1932-6203 ] ; 2012.
Abstract
The coxsackie- and adenovirus receptor (CAR) is a cell adhesion molecule predominantly associated with epithelial tight junctions in adult tissues. CAR is also expressed in cardiomyocytes and essential for heart development up to embryonic day 11.5, but not thereafter. CAR is not expressed in vascular endothelial cells but was recently detected in neonatal lymphatic vessels, suggesting that CAR could play a role in the development of the lymphatic system. To address this, we generated mice carrying a conditional deletion of the CAR gene (
Url:
DOI: 10.1371/journal.pone.0037523
PubMed: 22624044
PubMed Central: 3356332
Affiliations:
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sortKey="Pang, Mei Fong" sort="Pang, Mei Fong" uniqKey="Pang M" first="Mei-Fong" last="Pang">Mei-Fong Pang</name><affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>Vascular Biology Unit, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden</addr-line></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Vascular Biology Unit, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Zaini, Mohamad Amr" sort="Zaini, Mohamad Amr" uniqKey="Zaini M" first="Mohamad Amr" last="Zaini">Mohamad Amr Zaini</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Women's and Children's Health, Karolinska Institute and University Hospital, Stockholm, Sweden</addr-line></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Women's and Children's Health, Karolinska Institute and University Hospital, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Haiko, Paula" sort="Haiko, Paula" uniqKey="Haiko P" first="Paula" last="Haiko">Paula Haiko</name><affiliation wicri:level="4"><nlm:aff id="aff3"><addr-line>Molecular/Cancer Biology Laboratory, University of Helsinki, Helsinki, Finland</addr-line></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Laboratory, University of Helsinki, Helsinki</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName></affiliation></author><author><name sortKey="Tammela, Tuomas" sort="Tammela, Tuomas" uniqKey="Tammela T" first="Tuomas" last="Tammela">Tuomas Tammela</name><affiliation wicri:level="4"><nlm:aff id="aff3"><addr-line>Molecular/Cancer Biology Laboratory, University of Helsinki, Helsinki, Finland</addr-line></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Laboratory, University of Helsinki, Helsinki</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName></affiliation></author><author><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><affiliation wicri:level="4"><nlm:aff id="aff3"><addr-line>Molecular/Cancer Biology Laboratory, University of Helsinki, Helsinki, Finland</addr-line></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Laboratory, University of Helsinki, Helsinki</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName><orgName type="university">Université d'Helsinki</orgName></affiliation></author><author><name sortKey="Philipson, Lennart" sort="Philipson, Lennart" uniqKey="Philipson L" first="Lennart" last="Philipson">Lennart Philipson</name><affiliation wicri:level="3"><nlm:aff id="aff4"><addr-line>Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden</addr-line></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Cell and Molecular Biology, Karolinska Institute, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Fuxe, Jonas" sort="Fuxe, Jonas" uniqKey="Fuxe J" first="Jonas" last="Fuxe">Jonas Fuxe</name><affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>Vascular Biology Unit, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden</addr-line></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Vascular Biology Unit, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Sollerbrant, Kerstin" sort="Sollerbrant, Kerstin" uniqKey="Sollerbrant K" first="Kerstin" last="Sollerbrant">Kerstin Sollerbrant</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Women's and Children's Health, Karolinska Institute and University Hospital, Stockholm, Sweden</addr-line></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Women's and Children's Health, Karolinska Institute and University Hospital, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The coxsackie- and adenovirus receptor (CAR) is a cell adhesion molecule predominantly associated with epithelial tight junctions in adult tissues. CAR is also expressed in cardiomyocytes and essential for heart development up to embryonic day 11.5, but not thereafter. CAR is not expressed in vascular endothelial cells but was recently detected in neonatal lymphatic vessels, suggesting that CAR could play a role in the development of the lymphatic system. To address this, we generated mice carrying a conditional deletion of the CAR gene (<italic>Cxadr</italic>) and knocked out CAR in the mouse embryo at different time points during post-cardiac development. Deletion of <italic>Cxadr</italic> from E12.5, but not from E13.5, resulted in subcutaneous edema, hemorrhage and embryonic death. Subcutaneous lymphatic vessels were dilated and structurally abnormal with gaps and holes present at lymphatic endothelial cell-cell junctions. Furthermore, lymphatic vessels were filled with erythrocytes showing a defect in the separation between the blood and lymphatic systems. Regionally, erythrocytes leaked out into the interstitium from leaky lymphatic vessels explaining the hemorrhage detected in CAR-deficient mouse embryos. The results show that CAR plays an essential role in development of the lymphatic vasculature in the mouse embryo by promoting appropriate formation of lymphatic endothelial cell-cell junctions.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Bergelson, Jm" uniqKey="Bergelson J">JM Bergelson</name></author><author><name sortKey="Cunningham, Ja" uniqKey="Cunningham J">JA Cunningham</name></author><author><name sortKey="Droguett, G" uniqKey="Droguett G">G Droguett</name></author><author><name sortKey="Kurt Jones, Ea" uniqKey="Kurt Jones E">EA Kurt-Jones</name></author><author><name sortKey="Krithivas, A" uniqKey="Krithivas A">A Krithivas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tomko, Rp" uniqKey="Tomko R">RP Tomko</name></author><author><name sortKey="Xu, R" uniqKey="Xu R">R Xu</name></author><author><name sortKey="Philipson, L" uniqKey="Philipson L">L 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L">L Philipson</name></author><author><name sortKey="Fuxe, J" uniqKey="Fuxe J">J Fuxe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Othman, M" uniqKey="Othman M">M Othman</name></author><author><name sortKey="Labelle, A" uniqKey="Labelle A">A Labelle</name></author><author><name sortKey="Mazzetti, I" uniqKey="Mazzetti I">I Mazzetti</name></author><author><name sortKey="Elbatarny, Hs" uniqKey="Elbatarny H">HS Elbatarny</name></author><author><name sortKey="Lillicrap, D" uniqKey="Lillicrap D">D Lillicrap</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bertozzi, Cc" uniqKey="Bertozzi C">CC Bertozzi</name></author><author><name sortKey="Hess, Pr" uniqKey="Hess P">PR Hess</name></author><author><name sortKey="Kahn, Ml" uniqKey="Kahn M">ML Kahn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hayashi, S" uniqKey="Hayashi S">S Hayashi</name></author><author><name sortKey="Mcmahon, Ap" uniqKey="Mcmahon A">AP McMahon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Andersson, Am" uniqKey="Andersson A">AM Andersson</name></author><author><name sortKey="Pettersson, Rf" uniqKey="Pettersson R">RF Pettersson</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Finlande</li><li>Suède</li></country><region><li>Svealand</li><li>Uusimaa</li></region><settlement><li>Helsinki</li><li>Stockholm</li></settlement><orgName><li>Université d'Helsinki</li></orgName></list><tree><country name="Suède"><region name="Svealand"><name sortKey="Mirza, Momina" sort="Mirza, Momina" uniqKey="Mirza M" first="Momina" last="Mirza">Momina Mirza</name></region><name sortKey="Fuxe, Jonas" sort="Fuxe, Jonas" uniqKey="Fuxe J" first="Jonas" last="Fuxe">Jonas Fuxe</name><name sortKey="Pang, Mei Fong" sort="Pang, Mei Fong" uniqKey="Pang M" first="Mei-Fong" last="Pang">Mei-Fong Pang</name><name sortKey="Philipson, Lennart" sort="Philipson, Lennart" uniqKey="Philipson L" first="Lennart" last="Philipson">Lennart Philipson</name><name sortKey="Sollerbrant, Kerstin" sort="Sollerbrant, Kerstin" uniqKey="Sollerbrant K" first="Kerstin" last="Sollerbrant">Kerstin Sollerbrant</name><name sortKey="Zaini, Mohamad Amr" sort="Zaini, Mohamad Amr" uniqKey="Zaini M" first="Mohamad Amr" last="Zaini">Mohamad Amr Zaini</name></country><country name="Finlande"><region name="Uusimaa"><name sortKey="Haiko, Paula" sort="Haiko, Paula" uniqKey="Haiko P" first="Paula" last="Haiko">Paula Haiko</name></region><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><name sortKey="Tammela, Tuomas" sort="Tammela, Tuomas" uniqKey="Tammela T" first="Tuomas" last="Tammela">Tuomas Tammela</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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