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

Antanina Zmuidzinas, Klaus Dieter Fischer, Sergio A. Lira, Lesley Forrester, Sherri Bryant, Alan Bernstein, Mariano Barbacid

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

Previous studies have suggested that the vav proto-oncogene plays an important role in hematopoiesis. To study this further, we have ablated the vav proto-oncogene 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 (≥ 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 postimplantation embryos. These results suggest that the vav gene is essential for normal trophoblast development and for implantation of the developing embryo.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalEMBO Journal
Volume14
Issue number1
DOIs
StatePublished - 1995
Externally publishedYes

Keywords

  • Embryoid bodies
  • Gene targeting
  • Hematopoiesis
  • Implantation
  • Vav

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