Forsøksdyr: implantation of wnt-1 tumor cells in B6.129P2-Axltm1Dgen/J

Godkjenningsdato 11.01.2018

Axl is a member of the TAM (Tyro-Axl-Mer) receptor tyrosine kinases (RTK) transmembrane receptor tyrosine kinase. TAM family regulates whole range of cellular responses. Axl, particularly, is expressed in embryonic tissues and plays a role in the neural and mesenchymal development. In adult tissues its expression is restricted to smooth muscle cells. Relative to normal expression, increased level of Axl is specific for various disease states. In patients suffering from cancer Axl expression is associated with metastatic lesions and with poor overall patient survival. The B6.129P2-Axltm1Dgen/J mouse strain allows us to obtain a functional knockdown of Axl. The transgenic C57Bl6 Wnt-1 develop mammary tumors, by crossing this strain in an axl knockdown we have been able to assess the effect of the absence of axl in tumor development (project 6638). We showed a decrease of tumor incidence in axl knockout wnt-1 mice compared to axl expressing wnt-1 mice. The aim of the experiment is to understand the signalisation explaining this effect as well as the different cell populations involved. We would like to implant the wnt-1 dissociated cells in the mammary fat pad of axl knock out mice and compare with axl expressing mice. Moderate distress is expected, the implantation is done under gaz anesthesia, the solid tumors allow the mice to walk and to behave normally. The signalization underlying the results observed on project 6638 can better be done in the same conditions therefore in vivo experiment cannot be avoided because no in vitro conditions can involve all tumor cell populations in the same proportion. Based on previous projects we tried to reduce as possible the number of animals, the research groups are kept to 10 for almost all groups. For tail vein injection we increased the group to 15 because the wnt1 cells rarely metastasize. All harmful procedures will be done under anaesthesia and the experiment will be stopped before severe pain is observed (score sheet).