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In Vivo Characterization of Cardiac Tissue Defects Associated With Pdgfrα Gene Deletion In the Patch Mouse
Published online by Cambridge University Press: 02 July 2020
Extract
The active form of platelet derived growth factor (PDGF) is a polypeptide dimer of which there are three isoforms: PDGF-AA, PDGF-BB, and PDGF-AB. Furthermore, two types of PDGF receptors also exist: PDGFRα and PDGFRβ. The β-receptor binds only the PDGF-B chain with high affinity, while the αreceptor can bind either PDGF-A or -B chains. Both PDGF ligands and their receptors have been linked to such cellular responses as mitogenisis, cell migration, chemotaxis, adhesion and differentiation in a variety of cell types.
Several studies have reported fetal cardiac abnormalities associated with disruption of PDGF and its receptors. In spontaneous mutants lacking the PDGF α-receptor (Patchmice), fetal hearts are generally dilated and exhibit valve and outflow tract defects. Similar defects are observed in normal embryos injected with antibodies to block the functioning of the PDGF-A chain. Disruption of PDGF-B function results in ventricular and atrial dilation, reduction of the ventricular wall, and hyper-trabeculation.
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