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The vav proto-oncogene is required early in embryogenesis but not for hematopoietic development in vitro.

TitleThe vav proto-oncogene is required early in embryogenesis but not for hematopoietic development in vitro.
Publication TypeJournal Article
Year of Publication1995
AuthorsZmuidzinas A, Fischer KD, Lira SA, Forrester LM, Bryant S, Bernstein A, Barbacid M
JournalEMBO J
Date Published1995 Jan 3
KeywordsAnimals, Base Sequence, Cell Cycle Proteins, Cell Differentiation, Cells, Cultured, Embryo Implantation, Female, Gene Expression, Genes, Lethal, Hematopoiesis, Hematopoietic Stem Cells, Heterozygote, Homozygote, Mast Cells, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Mutation, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-vav, Stem Cells

Previous studies have suggested that the vav protooncogene plays an important role in hematopoiesis. To study this further, we have ablated the vav protooncogene by homologous recombination in embryonic stem (ES) cells. Homozygous vav (-/-) ES clones differentiate normally in culture and generate cells of erythroid, myeloid and mast cell lineages. Mice heterozygous for the targeted vav allele do not display any obvious abnormalities. However, homozygous embryos die very early during development. Crosses of vav (+/-) heterozygous mice yield apparently normal vav (-/-) E3.5 embryos but not post-implantation embryos (> or = E7.5). Furthermore, homozygous vav (-/-) blastocysts do not hatch in vitro. These results indicate that vav is essential for an early developmental step(s) that precedes the onset of hematopoiesis. Consistent with the phenotypic analysis of vav (-/-) embryos, we have identified Vav immunoreactivity in the extra-embryonic trophoblastic cell layer but not in the inner embryonic cell mass of E3.5 preimplantation embryos or in the egg cylinder of E6.5 and E7.5 post-implantation embryos. These results suggest that the vav gene is essential for normal trophoblast development and for implantation of the developing embryo.

Alternate JournalEMBO J.
PubMed ID7828581
PubMed Central IDPMC398046