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Conditional inactivation of VEGF-A in areas of collagen2a1 expression results in embryonic lethality in the heterozygous state

(2000) DEVELOPMENT. 127(7). p.1445-1453
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Abstract
VEGF-A has been implicated in regulating the initial angiogenic invasion events that are essential for endochondral bone formation. VEGF-A mRNA expression was indeed found in the sclerotome of the developing somite and in the limb-bud mesenchyme at E10.5 in mouse development but declined during chondrogenesis and became upregulated in hypertrophic chondrocytes prior to angiogenic invasion. To determine the functional importance of VEGF-A expression in the developing chondrogenic tissues, VEGF-A was conditionally inactivated during early embryonic development using Collagen2a1-Cre transgenic lines. Deletion of a single VEGF-A allele in Collagen2a1-Cre-expressing cells results in embryonic lethality around E10.5. This lethality is characterized by aberrant development of the dorsal aorta and intersomitic blood vessels, along with defects in the developing endocardial and myocardial layers of the heart. A small percentage of VEGF(Flox/)+, Collagen2a1-Cre fetuses survive until E17.5, show aberrant endochondral bone formation and develop a heart phenotype resembling a dilated form of ischemic cardiomyopathy, These results provide insights into the function of VEGF-A in heart and endochondral bone formation and underscore the importance of tightly controlled levels of VEGF-A during development.
Keywords
heart development, cardiomyopathy, conditional gene targeting, angiogenesis, cartilage, vascular endothelial growth factor (VEGF), collagen2a1, Cre/loxP, CARDIAC DEVELOPMENT, NEUREGULIN RECEPTOR, MICE LACKING, VASCULAR DEVELOPMENT, ENDOTHELIAL GROWTH-FACTOR, PLATE CARTILAGE, ANGIOGENESIS, REQUIREMENT, GENE, ANGIOPOIETIN-1

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Citation

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Chicago
Haigh, Jody, Hans-Peter Gerber, Napoleone Ferrara, and Erwin F Wagner. 2000. “Conditional Inactivation of VEGF-A in Areas of Collagen2a1 Expression Results in Embryonic Lethality in the Heterozygous State.” Development 127 (7): 1445–1453.
APA
Haigh, J., Gerber, H.-P., Ferrara, N., & Wagner, E. F. (2000). Conditional inactivation of VEGF-A in areas of collagen2a1 expression results in embryonic lethality in the heterozygous state. DEVELOPMENT, 127(7), 1445–1453.
Vancouver
1.
Haigh J, Gerber H-P, Ferrara N, Wagner EF. Conditional inactivation of VEGF-A in areas of collagen2a1 expression results in embryonic lethality in the heterozygous state. DEVELOPMENT. 2000;127(7):1445–53.
MLA
Haigh, Jody, Hans-Peter Gerber, Napoleone Ferrara, et al. “Conditional Inactivation of VEGF-A in Areas of Collagen2a1 Expression Results in Embryonic Lethality in the Heterozygous State.” DEVELOPMENT 127.7 (2000): 1445–1453. Print.
@article{1202130,
  abstract     = {VEGF-A has been implicated in regulating the initial angiogenic invasion events that are essential for endochondral bone formation. VEGF-A mRNA expression was indeed found in the sclerotome of the developing somite and in the limb-bud mesenchyme at E10.5 in mouse development but declined during chondrogenesis and became upregulated in hypertrophic chondrocytes prior to angiogenic invasion. To determine the functional importance of VEGF-A expression in the developing chondrogenic tissues, VEGF-A was conditionally inactivated during early embryonic development using Collagen2a1-Cre transgenic lines. Deletion of a single VEGF-A allele in Collagen2a1-Cre-expressing cells results in embryonic lethality around E10.5. This lethality is characterized by aberrant development of the dorsal aorta and intersomitic blood vessels, along with defects in the developing endocardial and myocardial layers of the heart. A small percentage of VEGF(Flox/)+, Collagen2a1-Cre fetuses survive until E17.5, show aberrant endochondral bone formation and develop a heart phenotype resembling a dilated form of ischemic cardiomyopathy, These results provide insights into the function of VEGF-A in heart and endochondral bone formation and underscore the importance of tightly controlled levels of VEGF-A during development.},
  author       = {Haigh, Jody and Gerber, Hans-Peter and Ferrara, Napoleone and Wagner, Erwin F},
  issn         = {0950-1991},
  journal      = {DEVELOPMENT},
  keyword      = {heart development,cardiomyopathy,conditional gene targeting,angiogenesis,cartilage,vascular endothelial growth factor (VEGF),collagen2a1,Cre/loxP,CARDIAC DEVELOPMENT,NEUREGULIN RECEPTOR,MICE LACKING,VASCULAR DEVELOPMENT,ENDOTHELIAL GROWTH-FACTOR,PLATE CARTILAGE,ANGIOGENESIS,REQUIREMENT,GENE,ANGIOPOIETIN-1},
  language     = {eng},
  number       = {7},
  pages        = {1445--1453},
  title        = {Conditional inactivation of VEGF-A in areas of collagen2a1 expression results in embryonic lethality in the heterozygous state},
  url          = {http://dev.biologists.org/content/127/7/1445.abstract},
  volume       = {127},
  year         = {2000},
}

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