Short and long-term effects of hVEGF-A(165) in cre-activated transgenic mice

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dc.contributor University of Helsinki, Translational Cancer Biology (TCB) Research Programme en
dc.contributor University of Helsinki, Helsingin biolääketieteellinen tutkijakoulu (-2009) en Leppänen, Pia Kholova, Ivana Mähönen, Anssi Airenne, Kari Koota, Suvi Mansukoski, Hannu Närvänen, Johanna Wirtzenius, Maria Alhonen, Leena Jänne, Juhani Alitalo, Kari Ylä-Herttuala, Seppo Wirzenius, Maria 2016-05-11T06:51:01Z 2016-05-11T06:51:01Z 2006
dc.identifier.citation Leppänen , P , Kholova , I , Mähönen , A , Airenne , K , Koota , S , Mansukoski , H , Närvänen , J , Wirtzenius , M , Alhonen , L , Jänne , J , Alitalo , K , Ylä-Herttuala , S & Wirzenius , M 2006 , ' Short and long-term effects of hVEGF-A(165) in cre-activated transgenic mice ' PLoS One , vol. 2006 , no. 1, e13, 8 s . DOI: 10.1371/journal.pone.0000013 en
dc.identifier.issn 1932-6203
dc.identifier.other PURE: 689388
dc.identifier.other PURE UUID: b990a552-1237-407c-b18b-3f46230dfc04
dc.identifier.other dawa_publication: 161185
dc.identifier.other WOS: 000207443600013
dc.identifier.other Scopus: 54449091655
dc.description.abstract We have generated a transgenic mouse where hVEGF-A(165) expression has been silenced with loxP-STOP fragment, and we used this model to study the effects of hVEGF-A(165) over-expression in mice after systemic adenovirus mediated Cre-gene transfer. Unlike previous conventional transgenic models, this model leads to the expression of hVEGF-A(165) in only a low number of cells in the target tissues in adult mice. Levels of hVEGF-A(165) expression were moderate and morphological changes were found mainly in the liver, showing typical signs of active angiogenesis. Most mice were healthy without any major consequences up to 18 months after the activation of hVEGF-A(165) expression. However, one mouse with a high plasma hVEGF-A(165) level died spontaneously because of bleeding into abdominal cavity and having liver hemangioma, haemorrhagic paratubarian cystic lesions and spleen peliosis. Also, two mice developed malignant tumors (hepatocellular carcinoma and lung adenocarcinoma), which were not seen in control mice. We conclude that long-term uncontrolled hVEGF-A(165) expression in only a limited number of target cells in adult mice can be associated with pathological changes, including possible formation of malignant tumors and uncontrolled bleeding in target tissues. These findings have implications for the design of long-term clinical trials using hVEGF-A(165) gene and protein. sv
dc.language.iso eng
dc.relation.ispartof PLoS One
dc.rights en
dc.title Short and long-term effects of hVEGF-A(165) in cre-activated transgenic mice en
dc.type Article
dc.description.version Peer reviewed
dc.type.uri info:eu-repo/semantics/other
dc.type.uri info:eu-repo/semantics/publishedVersion

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