Crim1KST264/KST264 mice implicate Crim1 in the regulation of vascular endothelial growth factor-A activity during glomerular vascular development.

Crim1KST264/KST264 mice implicate Crim1 in the regulation of vascular endothelial growth factor-A activity during glomerular vascular development. Research Abstract Details 

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Crim1KST264/KST264 mice implicate Crim1 in the regulation of vascular endothelial growth factor-A activity during glomerular vascular development. Abstract Text:

Lorine Wilkinson,Thierry Gilbert,Genevieve Kinna,Leah-Anne Ruta,David Pennisi,Michelle Kett,Melissa H Little,Lorine Wilkinson,Thierry Gilbert,Genevieve Kinna,Leah-Anne Ruta,David Pennisi,Michelle Kett,Melissa H Little,

Crim1, a transmembrane cysteine-rich repeat-containing protein that is related to chordin, plays a role in the tethering of growth factors at the cell surface. Crim1 is expressed in the developing kidney; in parietal cells, podocytes, and mesangial cells of the glomerulus; and in pericytes that surround the arterial vasculature. A gene-trap mouse line with an insertion in the Crim1 gene (Crim1(KST264/KST264)) displayed perinatal lethality with defects in multiple organ systems. This study further analyzed the defects that are present within the kidneys of these mice. Crim1(KST264/KST264) mice displayed abnormal glomerular development, illustrated by enlarged capillary loops, podocyte effacement, and mesangiolysis. When outbred, homozygotes that reached birth displayed podocyte and glomerular endothelial cell defects and marked albuminuria. The podocytic co-expression of Crim1 with vascular endothelial growth factor-A (VEGF-A) suggested a role for Crim1 in the regulation of VEGF-A action. Crim1 and VEGF-A were shown to interact directly, providing evidence that cysteine-rich repeat-containing proteins can bind to non-TGF-beta superfamily ligands. Crim1(KST264/KST264) mice display a mislocalization of VEGF-A within the developing glomerulus, as assessed by immunogold electron microscopy and increased activation of VEGF receptor 2 (Flk1) in the glomerular endothelial cells, suggesting that Crim1 regulates the delivery of VEGF-A by the podocytes to the endothelial cells. This is the first in vivo demonstration of regulation of VEGF-A delivery and supports the hypothesis that Crim1 functions to regulate the release of growth factors from the cell of synthesis.

Crim1KST264/KST264 mice implicate Crim1 in the regulation of vascular endothelial growth factor-A activity during glomerular vascular development. Publishing Authors By Initials

L Wilkinson,T Gilbert,G Kinna,LA Ruta,D Pennisi,M Kett,MH Little,L Wilkinson,T Gilbert,G Kinna,LA Ruta,D Pennisi,M Kett,MH Little,

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Crim1KST264/KST264 mice implicate Crim1 in the regulation of vascular endothelial growth factor-A activity during glomerular vascular development. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of the American Society of Nephrology : JA

VOLUME: 18

Page Numbers: 1697-708

Journal Abbreviation: J. Am. Soc. Nephrol.

ISSN: 1046-6673

DAY: 25

MONTH: 04

YEAR: 2007

Crim1KST264/KST264 mice implicate Crim1 in the regulation of vascular endothelial growth factor-A activity during glomerular vascular development. Information

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LANGUAGE: eng

NlmUniqueID: 9013836

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Grant and Affiliation Information for Crim1KST264/KST264 mice implicate Crim1 in the regulation of vascular endothelial growth factor-A activity during glomerular vascular development.

AFFILIATION: Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia 4072.

Country: United States

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MEDLINETA: J Am Soc Nephrol

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