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Proc Natl Acad Sci U S A. 1994 Dec 20; 91(26): 12755–12759.
doi: 10.1073/pnas.91.26.12755
PMCID: PMC45518
PMID: 7809116

Hematopoietic development of vav-/- mouse embryonic stem cells.

R Zhang, F Y Tsai, and S H Orkin
Author information Copyright and License information PMC Disclaimer

Abstract

The vav protooncogene product is expressed nearly exclusively in hematopoietic lineages and contains several structural motifs (SH2/SH3 domains and a dbl-oncogene homology region) typical of proteins functioning in signaling pathways. To ascertain if vav expression is required for hematopoiesis we generated vav-negative mouse embryonic stem cells by gene targeting and examined the consequences of loss of vav function on erythroid and myeloid development in vitro and in vivo. In conflict with the conclusions drawn from expression of antisense vav RNA in embryonic stem cells [Wulf, G. M., Adra, C. N. & Lim, B. (1993) EMBO J. 12, 5065-5074], we observed erythroid and myeloid development in the absence of vav. These experiments demonstrate that vav expression is not absolutely required for hematopoietic development.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  • Katzav S, Martin-Zanca D, Barbacid M. vav, a novel human oncogene derived from a locus ubiquitously expressed in hematopoietic cells. EMBO J. 1989 Aug;8(8):2283–2290. [PMC free article] [PubMed] [Google Scholar]
  • Katzav S. vav: a molecule for all haemopoiesis? Br J Haematol. 1992 Jun;81(2):141–144. [PubMed] [Google Scholar]
  • Adams JM, Houston H, Allen J, Lints T, Harvey R. The hematopoietically expressed vav proto-oncogene shares homology with the dbl GDP-GTP exchange factor, the bcr gene and a yeast gene (CDC24) involved in cytoskeletal organization. Oncogene. 1992 Apr;7(4):611–618. [PubMed] [Google Scholar]
  • Boguski MS, Bairoch A, Attwood TK, Michaels GS. Proto-vav and gene expression. Nature. 1992 Jul 9;358(6382):113–113. [PubMed] [Google Scholar]
  • Bustelo XR, Ledbetter JA, Barbacid M. Product of vav proto-oncogene defines a new class of tyrosine protein kinase substrates. Nature. 1992 Mar 5;356(6364):68–71. [PubMed] [Google Scholar]
  • Margolis B, Hu P, Katzav S, Li W, Oliver JM, Ullrich A, Weiss A, Schlessinger J. Tyrosine phosphorylation of vav proto-oncogene product containing SH2 domain and transcription factor motifs. Nature. 1992 Mar 5;356(6364):71–74. [PubMed] [Google Scholar]
  • Bustelo XR, Barbacid M. Tyrosine phosphorylation of the vav proto-oncogene product in activated B cells. Science. 1992 May 22;256(5060):1196–1199. [PubMed] [Google Scholar]
  • Evans GA, Howard OM, Erwin R, Farrar WL. Interleukin-2 induces tyrosine phosphorylation of the vav proto-oncogene product in human T cells: lack of requirement for the tyrosine kinase lck. Biochem J. 1993 Sep 1;294(Pt 2):339–342. [PMC free article] [PubMed] [Google Scholar]
  • Alai M, Mui AL, Cutler RL, Bustelo XR, Barbacid M, Krystal G. Steel factor stimulates the tyrosine phosphorylation of the proto-oncogene product, p95vav, in human hemopoietic cells. J Biol Chem. 1992 Sep 5;267(25):18021–18025. [PubMed] [Google Scholar]
  • Gulbins E, Coggeshall KM, Baier G, Katzav S, Burn P, Altman A. Tyrosine kinase-stimulated guanine nucleotide exchange activity of Vav in T cell activation. Science. 1993 May 7;260(5109):822–825. [PubMed] [Google Scholar]
  • Bustelo XR, Suen KL, Leftheris K, Meyers CA, Barbacid M. Vav cooperates with Ras to transform rodent fibroblasts but is not a Ras GDP/GTP exchange factor. Oncogene. 1994 Aug;9(8):2405–2413. [PubMed] [Google Scholar]
  • Burkert U, von Rüden T, Wagner EF. Early fetal hematopoietic development from in vitro differentiated embryonic stem cells. New Biol. 1991 Jul;3(7):698–708. [PubMed] [Google Scholar]
  • Schmitt RM, Bruyns E, Snodgrass HR. Hematopoietic development of embryonic stem cells in vitro: cytokine and receptor gene expression. Genes Dev. 1991 May;5(5):728–740. [PubMed] [Google Scholar]
  • Wiles MV, Keller G. Multiple hematopoietic lineages develop from embryonic stem (ES) cells in culture. Development. 1991 Feb;111(2):259–267. [PubMed] [Google Scholar]
  • Keller G, Kennedy M, Papayannopoulou T, Wiles MV. Hematopoietic commitment during embryonic stem cell differentiation in culture. Mol Cell Biol. 1993 Jan;13(1):473–486. [PMC free article] [PubMed] [Google Scholar]
  • Pevny L, Simon MC, Robertson E, Klein WH, Tsai SF, D'Agati V, Orkin SH, Costantini F. Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1. Nature. 1991 Jan 17;349(6306):257–260. [PubMed] [Google Scholar]
  • Wulf GM, Adra CN, Lim B. Inhibition of hematopoietic development from embryonic stem cells by antisense vav RNA. EMBO J. 1993 Dec 15;12(13):5065–5074. [PMC free article] [PubMed] [Google Scholar]
  • Tybulewicz VL, Crawford CE, Jackson PK, Bronson RT, Mulligan RC. Neonatal lethality and lymphopenia in mice with a homozygous disruption of the c-abl proto-oncogene. Cell. 1991 Jun 28;65(7):1153–1163. [PubMed] [Google Scholar]
  • Mansour SL, Thomas KR, Capecchi MR. Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes. Nature. 1988 Nov 24;336(6197):348–352. [PubMed] [Google Scholar]
  • Mortensen RM, Conner DA, Chao S, Geisterfer-Lowrance AA, Seidman JG. Production of homozygous mutant ES cells with a single targeting construct. Mol Cell Biol. 1992 May;12(5):2391–2395. [PMC free article] [PubMed] [Google Scholar]
  • Robertson E, Bradley A, Kuehn M, Evans M. Germ-line transmission of genes introduced into cultured pluripotential cells by retroviral vector. Nature. 1986 Oct 2;323(6087):445–448. [PubMed] [Google Scholar]
  • Weiss MJ, Keller G, Orkin SH. Novel insights into erythroid development revealed through in vitro differentiation of GATA-1 embryonic stem cells. Genes Dev. 1994 May 15;8(10):1184–1197. [PubMed] [Google Scholar]
  • Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [PubMed] [Google Scholar]
  • McClanahan T, Dalrymple S, Barkett M, Lee F. Hematopoietic growth factor receptor genes as markers of lineage commitment during in vitro development of hematopoietic cells. Blood. 1993 Jun 1;81(11):2903–2915. [PubMed] [Google Scholar]
  • Royer-Pokora B, Kunkel LM, Monaco AP, Goff SC, Newburger PE, Baehner RL, Cole FS, Curnutte JT, Orkin SH. Cloning the gene for an inherited human disorder--chronic granulomatous disease--on the basis of its chromosomal location. Nature. 1986 Jul 3;322(6074):32–38. [PubMed] [Google Scholar]
  • Harris N, Super M, Rits M, Chang G, Ezekowitz RA. Characterization of the murine macrophage mannose receptor: demonstration that the downregulation of receptor expression mediated by interferon-gamma occurs at the level of transcription. Blood. 1992 Nov 1;80(9):2363–2373. [PubMed] [Google Scholar]
  • te Riele H, Maandag ER, Clarke A, Hooper M, Berns A. Consecutive inactivation of both alleles of the pim-1 proto-oncogene by homologous recombination in embryonic stem cells. Nature. 1990 Dec 13;348(6302):649–651. [PubMed] [Google Scholar]
  • Capecchi MR. Altering the genome by homologous recombination. Science. 1989 Jun 16;244(4910):1288–1292. [PubMed] [Google Scholar]
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