Document Detail

VEGF: a modifier of the del22q11 (DiGeorge) syndrome?
MedLine Citation:
PMID:  12539040     Owner:  NLM     Status:  MEDLINE    
Hemizygous deletion of chromosome 22q11 (del22q11) causes thymic, parathyroid, craniofacial and life-threatening cardiovascular birth defects in 1 in 4,000 infants. The del22q11 syndrome is likely caused by haploinsufficiency of TBX1, but its variable expressivity indicates the involvement of additional modifiers. Here, we report that absence of the Vegf164 isoform caused birth defects in mice, reminiscent of those found in del22q11 patients. The close correlation of birth and vascular defects indicated that vascular dysgenesis may pathogenetically contribute to the birth defects. Vegf interacted with Tbx1, as Tbx1 expression was reduced in Vegf164-deficient embryos and knocked-down vegf levels enhanced the pharyngeal arch artery defects induced by tbx1 knockdown in zebrafish. Moreover, initial evidence suggested that a VEGF promoter haplotype was associated with an increased risk for cardiovascular birth defects in del22q11 individuals. These genetic data in mouse, fish and human indicate that VEGF is a modifier of cardiovascular birth defects in the del22q11 syndrome.
Ingeborg Stalmans; Diether Lambrechts; Frederik De Smet; Sandra Jansen; Jian Wang; Sunit Maity; Paige Kneer; Maren von der Ohe; Ann Swillen; Christa Maes; Marc Gewillig; Daniel G M Molin; Peter Hellings; Thurid Boetel; Maartin Haardt; Veerle Compernolle; Mieke Dewerchin; Stephane Plaisance; Robert Vlietinck; Beverly Emanuel; Adriana C Gittenberger-de Groot; Peter Scambler; Bernice Morrow; Deborah A Driscol; Lieve Moons; Camila V Esguerra; Geert Carmeliet; Annett Behn-Krappa; Koen Devriendt; Désiré Collen; Simon J Conway; Peter Carmeliet
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2003-01-21
Journal Detail:
Title:  Nature medicine     Volume:  9     ISSN:  1078-8956     ISO Abbreviation:  Nat. Med.     Publication Date:  2003 Feb 
Date Detail:
Created Date:  2003-02-03     Completed Date:  2003-05-09     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9502015     Medline TA:  Nat Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  173-82     Citation Subset:  IM    
The Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Katholieke Universiteit Leuven, Leuven, Belgium.
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MeSH Terms
Blood Vessels / abnormalities
Chromosome Deletion*
Congenital Abnormalities / genetics
DiGeorge Syndrome / genetics*
Endothelial Growth Factors / genetics*
Face / abnormalities
Intercellular Signaling Peptides and Proteins / genetics*
Lymphokines / genetics*
Mice, Knockout
Neuropilin-1 / genetics
Protein Isoforms / genetics
Skull / abnormalities
T-Box Domain Proteins / genetics
Thymus Gland / abnormalities
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Grant Support
Reg. No./Substance:
0/Endothelial Growth Factors; 0/Intercellular Signaling Peptides and Proteins; 0/Lymphokines; 0/Protein Isoforms; 0/T-Box Domain Proteins; 0/Tbx1 protein, mouse; 0/Vascular Endothelial Growth Factor A; 0/Vascular Endothelial Growth Factors; 144713-63-3/Neuropilin-1

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