Embryonic lethalities and endothelial tumors in chimeric mice expressing polyoma virus middle T oncogene

R. Lindsay Williams, Sara A. Courtneidge, Erwin F. Wagner

Research output: Contribution to journalArticlepeer-review

192 Scopus citations

Abstract

The effect of the middle T oncogene of polyoma virus was studied in vivo using a replication-defective selectable retrovirus. Injection of virus into newborn and adult mice resulted in the rapid appearance of cavernous hemangiomas. Infection of embryos did not yield transgenic mice; therefore, embryonal stem (ES) cells were used as an alternative system. Several infected ES cell clones were established that constitutively expressed middle T and its associated tyrosine kinase activity. Chimeric embryos obtained by blastocyst injection of individual ES cell clones were specifically arrested at midgestation, when multiple hemangiomas disrupted blood vessel formation. From these tumors endothelial cell lines were established that retained expression of von Willebrand factor yet were tumorigenic in vivo. These results suggest that middle T acts in endothelial cells as a single-step oncogene and that ES cells provide a valuable system for the study of growth control during embryogenesis.

Original languageEnglish (US)
Pages (from-to)121-131
Number of pages11
JournalCell
Volume52
Issue number1
DOIs
StatePublished - Jan 15 1988
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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