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PMID: 15882861 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Dosage-dependent requirement for mouse Vezf1 in vascular system development.

Developmental biology ·Vol. 283 ·No. 1 ·2005-07-01 ·Pages 140-56

Kuhnert F, Campagnolo L, Xiong JW, Lemons D, Fitch MJ, Zou Z, Kiosses WB, Gardner H, Stuhlmann H

Abstract

Vezf1 is an early development gene that encodes a zinc finger transcription factor. In the developing embryo, Vezf1 is expressed in the yolk sac mesoderm and the endothelium of the developing vasculature and, in addition, in mesodermal and neuronal tissues. Targeted inactivation of Vezf1 in mice reveals that it acts in a closely regulated, dose-dependent fashion on the development of the blood vascular and lymphatic system. Homozygous mutant embryos display vascular remodeling defects and loss of vascular integrity leading to localized hemorrhaging. Ultrastructural analysis shows defective endothelial cell adhesion and tight junction formation in the mutant vessels. Moreover, in heterozygous embryos, haploinsufficiency is observed that is characterized by lymphatic hypervascularization associated with hemorrhaging and edema in the jugular region; a phenotype reminiscent of the human congenital lymphatic malformation syndrome cystic hygroma.

MeSH Terms
Animals Base Sequence Blood Vessels/abnormalities,embryology Cloning, Molecular DNA Primers DNA-Binding Proteins Embryonic Development Endothelium, Vascular/abnormalities,embryology Gene Dosage Gene Expression Regulation, Developmental Genotype Kruppel-Like Transcription Factors Mesoderm/physiology Mice Mice, Knockout Neovascularization, Physiologic Polymerase Chain Reaction Transcription Factors/deficiency,genetics Yolk Sac/physiology
Chemicals
DNA Primers DNA-Binding Proteins Kruppel-Like Transcription Factors Transcription Factors Vezf1 protein, mouse
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Kuhnert Frank
Department of Cell Biology, Division of Vascular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Campagnolo Luisa
Xiong Jing-Wei
Lemons Derek
Fitch Michael J
Zou Zhongmin
Kiosses William B
Gardner Humphrey
Stuhlmann Heidi
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Article Info
Journal
Developmental biology
Abbr.
Dev Biol
ISSN
0012-1606
DOI
10.1016/j.ydbio.2005.04.003
Published
2005-07-01
Pages
140-56
Language
English
Region
United States
NLM ID
0372762
PMCID
PMC1453095
Subset
IM
Grants
NHLBI NIH HHS · R01 HL065738 · United States
NICHD NIH HHS · R29 HD31534 · United States
NHLBI NIH HHS · R01 HL65738 · United States
NIDDK NIH HHS · T32 DK07757 · United States
NIDDK NIH HHS · T32 DK007757 · United States
External Links
PubMed source DOI: 10.1016/j.ydbio.2005.04.003 PMC Full Text View journal details
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