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Development, Vol 121, Issue 6 1845-1854, Copyright © 1995 by Company of Biologists

JOURNAL ARTICLES

Defective haematopoiesis and vasculogenesis in transforming growth factor-beta 1 knock out mice

MC Dickson, JS Martin, FM Cousins, AB Kulkarni, S Karlsson and RJ Akhurst
Department of Medical Genetics, University of Glasgow, Duncan Guthrie Institute, Yorkhill, UK.

Transforming growth factor beta 1 (TGF beta 1) is shown here to be required for yolk sac haematopoiesis and endothelial differentiation. Mice with a targeted mutation in the TGF beta 1 gene were examined to determine the cause of prenatal lethality, which occurs in 50% of homozygous TGF beta 1 null (TGF beta 1-/-) conceptions. 50% of TGF beta 1-/- and 25% of TGF beta 1-+-) conceptions. 50% of TGF beta 1-/- and 25% of TGF beta 1+/- conceptuses were found to die at around 10.5 dpc. The primary defects were restricted to extraembryonic tissues, namely the yolk sac vasculature and haematopoietic system. The embryos per se showed developmental retardation, oedema and necrosis, which were probably secondary to the extraembryonic lesions. The defect in vasculogenesis appeared to affect endothelial differentiation, rather than the initial appearance and outgrowth of endothelial cells. Initial differentiation of yolk sac mesoderm to endothelial cells occurred, but defective differentiation resulted in inadequate capillary tube formation, and weak vessels with reduced cellular adhesiveness. Defective haematopoiesis resulted in a reduced erythroid cell number within the yolk sac. Defective yolk sac vasculogenesis and haematopoiesis were present either together, or in isolation of each other. The phenotypes are consistent with the observation of abundant TGF beta 1 gene expression in both endothelial and haematopoietic precursors. The data indicate that the primary effect of loss of TGF beta 1 function in vivo is not increased haematopoietic or endothelial cell proliferation, which might have been expected by deletion of a negative growth regulator, but defective haematopoiesis and endothelial differentiation.
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[Abstract] [Full Text] [PDF]

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 Hum Mol GenetHome page
Y. Tang, M. L. McKinnon, L. M. Leong, S. A. B. Rusholme, S. Wang, and R. J. Akhurst
Genetic modifiers interact with maternal determinants in vascular development of Tgfb1-/- mice
Hum. Mol. Genet., July 1, 2003; 12(13): 1579 - 1589.
[Abstract] [Full Text] [PDF]

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 FASEB J.Home page
N. A. TAYLOR, W. J. M. VAN DE VEN, and J. W. M. CREEMERS
Curbing activation: proprotein convertases in homeostasis and pathology
FASEB J, July 1, 2003; 17(10): 1215 - 1227.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. Biol.Home page
K. L. Stenvers, M. L. Tursky, K. W. Harder, N. Kountouri, S. Amatayakul-Chantler, D. Grail, C. Small, R. A. Weinberg, A. M. Sizeland, and H.-J. Zhu
Heart and Liver Defects and Reduced Transforming Growth Factor {beta}2 Sensitivity in Transforming Growth Factor {beta} Type III Receptor-Deficient Embryos
Mol. Cell. Biol., June 15, 2003; 23(12): 4371 - 4385.
[Abstract] [Full Text] [PDF]

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 CROBMHome page
T. Thyagarajan, S. Totey, M. J. S. Danton, and A. B. Kulkarni
GENETICALLY ALTERED MOUSE MODELS: THE GOOD, THE BAD, AND THE UGLY
Critical Reviews in Oral Biology & Medicine, May 1, 2003; 14(3): 154 - 174.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
R. Bommireddy, V. Saxena, I. Ormsby, M. Yin, G. P. Boivin, G. F. Babcock, R. R. Singh, and T. Doetschman
TGF-{beta}1 Regulates Lymphocyte Homeostasis by Preventing Activation and Subsequent Apoptosis of Peripheral Lymphocytes
J. Immunol., May 1, 2003; 170(9): 4612 - 4622.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
R. Bommireddy, I. Ormsby, M. Yin, G. P. Boivin, G. F. Babcock, and T. Doetschman
TGF{beta}1 Inhibits Ca2+-Calcineurin-Mediated Activation in Thymocytes
J. Immunol., April 1, 2003; 170(7): 3645 - 3652.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
S. van den Driesche, C. L. Mummery, and C. J.J. Westermann
Hereditary hemorrhagic telangiectasia: an update on transforming growth factor {beta} signaling in vasculogenesis and angiogenesis
Cardiovasc Res, April 1, 2003; 58(1): 20 - 31.
[Abstract] [Full Text] [PDF]

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 BloodHome page
H. Zhang, H. O. Akman, E. L. P. Smith, J. Zhao, J. E. Murphy-Ullrich, and O. A. Batuman
Cellular response to hypoxia involves signaling via Smad proteins
Blood, March 15, 2003; 101(6): 2253 - 2260.
[Abstract] [Full Text] [PDF]

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 DevelopmentHome page
J. Zhu, K. Motejlek, D. Wang, K. Zang, A. Schmidt, and L. F. Reichardt
{beta}8 integrins are required for vascular morphogenesis in mouse embryos
Development, March 8, 2003; 129(12): 2891 - 2903.
[Abstract] [Full Text] [PDF]

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 DevelopmentHome page
B. L. Roman, V. N. Pham, N. D. Lawson, M. Kulik, S. Childs, A. C. Lekven, D. M. Garrity, R. T. Moon, M. C. Fishman, R. J. Lechleider, et al.
Disruption of acvrl1 increases endothelial cell number in zebrafish cranial vessels
Development, March 8, 2003; 129(12): 3009 - 3019.
[Abstract] [Full Text] [PDF]

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 DevelopmentHome page
S. S. Gerety and D. J. Anderson
Cardiovascular ephrinB2 function is essential for embryonic angiogenesis
Development, March 5, 2003; 129(6): 1397 - 1410.
[Abstract] [Full Text] [PDF]

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 CROBMHome page
Y. Chai, Y. Ito, and J. Han
TGF-{beta} SIGNALING AND ITS FUNCTIONAL SIGNIFICANCE IN REGULATING THE FATE OF CRANIAL NEURAL CREST CELLS
Critical Reviews in Oral Biology & Medicine, March 1, 2003; 14(2): 78 - 88.
[Abstract] [Full Text] [PDF]

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 Am. J. Pathol.Home page
C. Bondjers, M. Kalen, M. Hellstrom, S. J. Scheidl, A. Abramsson, O. Renner, P. Lindahl, H. Cho, J. Kehrl, and C. Betsholtz
Transcription Profiling of Platelet-Derived Growth Factor-B-Deficient Mouse Embryos Identifies RGS5 as a Novel Marker for Pericytes and Vascular Smooth Muscle Cells
Am. J. Pathol., March 1, 2003; 162(3): 721 - 729.
[Abstract] [Full Text] [PDF]

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 Clin Med ResHome page
K. C. Flanders and J. K. Burmester
Medical Applications of Transforming Growth Factor-{beta}
Clin. Med. Res., January 1, 2003; 1(1): 13 - 20.
[Abstract] [Full Text] [PDF]

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 BloodHome page
B. Liu, Y. Sun, F. Jiang, S. Zhang, Y. Wu, Y. Lan, X. Yang, and N. Mao
Disruption of Smad5 gene leads to enhanced proliferation of high-proliferative potential precursors during embryonic hematopoiesis
Blood, January 1, 2003; 101(1): 124 - 133.
[Abstract] [Full Text] [PDF]

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 Endocr. Rev.Home page
H. Chang, C. W. Brown, and M. M. Matzuk
Genetic Analysis of the Mammalian Transforming Growth Factor-{beta} Superfamily
Endocr. Rev., December 1, 2002; 23(6): 787 - 823.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
A. Rodriguez-Pena, N. Eleno, A. Duwell, M. Arevalo, F. Perez-Barriocanal, O. Flores, N. Docherty, C. Bernabeu, M. Letarte, and J. M. Lopez-Novoa
Endoglin Upregulation During Experimental Renal Interstitial Fibrosis in Mice
Hypertension, November 1, 2002; 40(5): 713 - 720.
[Abstract] [Full Text] [PDF]

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 Physiol. GenomicsHome page
P. I. Teng, M. R. Dichiara, L. G. Komuves, K. Abe, T. Quertermous, and J. N. Topper
Inducible and selective transgene expression in murine vascular endothelium
Physiol Genomics, October 29, 2002; 11(2): 99 - 107.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
A. H. Shah, W. B. Tabayoyong, S. Y. Kimm, S.-J. Kim, L. van Parijs, and C. Lee
Reconstitution of Lethally Irradiated Adult Mice with Dominant Negative TGF-{beta} Type II Receptor-Transduced Bone Marrow Leads to Myeloid Expansion and Inflammatory Disease
J. Immunol., October 1, 2002; 169(7): 3485 - 3491.
[Abstract] [Full Text] [PDF]

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 Mol. Biol. CellHome page
A. Nishihara, T. Watabe, T. Imamura, and K. Miyazono
Functional Heterogeneity of Bone Morphogenetic Protein Receptor-II Mutants Found in Patients with Primary Pulmonary Hypertension
Mol. Biol. Cell, September 1, 2002; 13(9): 3055 - 3063.
[Abstract] [Full Text] [PDF]

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 IOVSHome page
W. Schacke, K.-F. Beck, J. Pfeilschifter, F. Koch, and L.-O. Hattenbach
Modulation of Tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 by Transforming Growth Factor-{beta} in Human Retinal Glial Cells
Invest. Ophthalmol. Vis. Sci., August 1, 2002; 43(8): 2799 - 2805.
[Abstract] [Full Text] [PDF]

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 BloodHome page
H. Miyashita, T. Yamazaki, T. Akada, O. Niizeki, M. Ogawa, S.-i. Nishikawa, and Y. Sato
A mouse orthologue of puromycin-insensitive leucyl-specific aminopeptidase is expressed in endothelial cells and plays an important role in angiogenesis
Blood, May 1, 2002; 99(9): 3241 - 3249.
[Abstract] [Full Text] [PDF]

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 Jpn J Clin OncolHome page
H. Sasaki, Y. Kobayashi, Y. Nakashima, S. Moriyama, H. Yukiue, M. Kaji, M. Kiriyama, I. Fukai, Y. Yamakawa, and Y. Fujii
{beta}IGH3, a TGF-{beta} Inducible Gene, is Overexpressed in Lung Cancer
Jpn. J. Clin. Oncol., March 1, 2002; 32(3): 85 - 89.
[Abstract] [Full Text] [PDF]

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 Exp. Biol. Med.Home page
J. P. Grande, G. M. Warner, H. J. Walker, A. N. K. Yusufi, J. Cheng, C. E. Gray, J. B. Kopp, and K. A. Nath
TGF-{beta}1 Is an Autocrine Mediator of Renal Tubular Epithelial Cell Growth and Collagen IV Production
Experimental Biology and Medicine, March 1, 2002; 227(3): 171 - 181.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
K. K. Hirschi, L. Lai, N. S. Belaguli, D. A. Dean, R. J. Schwartz, and W. E. Zimmer
Transforming Growth Factor-beta Induction of Smooth Muscle Cell Phenotpye Requires Transcriptional and Post-transcriptional Control of Serum Response Factor
J. Biol. Chem., February 15, 2002; 277(8): 6287 - 6295.
[Abstract] [Full Text] [PDF]

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 Cold Spring Harb Symp Quant BiolHome page
R.O. HYNES, J.C. LIVELY, J.H. MCCARTY, D. TAVERNA, S.E. FRANCIS, K. HODIVALA-DILKE, and Q. XIAO
The Diverse Roles of Integrins and Their Ligands in Angiogenesis
Cold Spring Harb Symp Quant Biol, January 1, 2002; 67(0): 143 - 154.
[Abstract] [PDF]

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 BloodHome page
S. K. Cho, A. Bourdeau, M. Letarte, and J. C. Zuniga-Pflucker
Expression and function of CD105 during the onset of hematopoiesis from Flk1+ precursors
Blood, December 15, 2001; 98(13): 3635 - 3642.
[Abstract] [Full Text] [PDF]

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 BloodHome page
H. O. Akman, H. Zhang, M. A. Q. Siddiqui, W. Solomon, E. L. P. Smith, and O. A. Batuman
Response to hypoxia involves transforming growth factor-beta 2 and Smad proteins in human endothelial cells
Blood, December 1, 2001; 98(12): 3324 - 3331.
[Abstract] [Full Text] [PDF]


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