The generation and in vivo differentiation of murine embryonal stem cells genetically null for either N-cadherin or N- and P-cadherin

Many mutations of the murine genome are recessive embryonic lethals preclud ing phenotype analysis at subsequent stages of development. This is true fo r embryos genetically lacking either N-cadherin or N- and P-cadherin. To ci rcumvent this, we have generated pluripotent embryonal stem (ES) cells of t he same genotype in vitro and differentiated them in vivo in the form of te ratomas. All of the ES cells isolated in this study had a normal ES cell mo rphology in vitro and were able to generate teratomas. Histological analysi s revealed that some differentiation and histogenesis had occurred within t he teratomas. Epithelial formation was, for example, unaffected in all cadh erin null cells. Surprisingly, however, the differentiation of cells lackin g both N- and P-cadherin was, in general, even more pronounced both quantit atively and qualitatively. Tumours lacking either N- cadherin or N- and P-c adherin contained more striated muscle (apparently cardiac muscle) than het erozygote controls, and this was most strikingly conspicuous in teratomas f rom N- and P-cadherin null cells. This more pronounced differentiation was not seen for all tissues, however, as structures with a simple neural tube- like morphology were never found in teratomas lacking both N- and P-cadheri n and organoid-like structures were rare in Ncad-/-tissue.