The aim of our group is to identify Protein kinase C in vivo function by analysing individual PKC knock outs we have generated over the past few years. The general approach we are using to identify target tissues and/or defined cell populations within the mouse for further investigation is a detailed expression analysis of individual PKC isoforms. For these purposes we have established several specific tools in the past which allows us to follow up isoform specific PKC expression on a very precise level. Doing so we have started to investigate PKC expression profiles under various tumour conditions in mice. As predicted we were able to identify various PKC isoforms to be either up or down regulated during the development and progression of certain tumours implying that these isoforms are substantially linked to the biology of these tumours. In order to proof this hypothesis we then cross relevant PKC knock out lines on the appropiate tumour background and analyse tumour growth and progression under PKC deficient conditions. Examplary for this approach recent data of PKCalpha deficient APCmin mice will be presented. Along the line of isoform specific PKC expression profiles we also identified various tissues and cell population with overlapping PKC expression without showing a phenotyp in the single knock out raising the question whether there is redundancy within the PKC family. To address this question we have started to generate PKC double knock outs and in fact some combinations clearly show phenotyps not present in the single knock out indicating that compensation takes place among PKC isoforms. Recent data will be presented.
Life Sciences 2007 (2007) Proc Life Sciences, SA225
Research Symposium: Functional PKC in vivo analysis using deficient mouse models
M. Leitges1
1. Biotechnology Center Oslo, Oslo, Norway.
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Where applicable, experiments conform with Society ethical requirements.