Loss of renal microvascular integrity in postnatal Crim1 hypomorphic transgenic mice

Wilkinson, L, Gilbert, T, Sipos, A, Toma, I, Pennisi, D. J., Peti-Peterdi, J and Little, M. H. (2009) Loss of renal microvascular integrity in postnatal Crim1 hypomorphic transgenic mice. KIDNEY INTERNATIONAL, 76 11: 1161-1171. doi:10.1038/ki.2009.345

Author Wilkinson, L
Gilbert, T
Sipos, A
Toma, I
Pennisi, D. J.
Peti-Peterdi, J
Little, M. H.
Title Loss of renal microvascular integrity in postnatal Crim1 hypomorphic transgenic mice
Journal name KIDNEY INTERNATIONAL   Check publisher's open access policy
ISSN 0085-2538
Publication date 2009-12
Year available 2009
Sub-type Article (original research)
DOI 10.1038/ki.2009.345
Volume 76
Issue 11
Start page 1161
End page 1171
Total pages 11
Editor Radha McLean
Place of publication London , U.K.
Publisher Nature Publishing Group
Collection year 2010
Language eng
Subject C1
970111 Expanding Knowledge in the Medical and Health Sciences
060499 Genetics not elsewhere classified
Abstract Crim1 is a cell-surface, transmembrane protein that binds to a variety of cystine knot–containing growth factors, including vascular endothelial growth factor A. In the developing renal glomerulus, Crim1 acts to tether vascular endothelial growth factor A to the podocyte cell surface, thus regulating its release to glomerular endothelial cells. The hypomorphic transgenic mouse (Crim1KST264/KST264) has glomerular cysts and severe glomerular vascular defects because of the lack of functional Crim1 in the glomerulus. Adult transgenic mice have a reduced glomerular filtration rate and glomerular capillary defects. We now show that, in these adult transgenic mice, renal vascular defects are not confined to the glomerulus but also extend to the peritubular microvasculature, as live imaging revealed leakiness of both glomerular and peritubular capillaries. An ultrastructural analysis of the microvasculature showed an abnormal endothelium and collagen deposition between the endothelium and the tubular basement membrane, present even in juvenile mice. Overt renal disease, including fibrosis and renin recruitment, was not evident until adulthood. Our study suggests that Crim1 is involved in endothelial maintenance and integrity and its loss contributes to a primary defect in the extraglomerular vasculature.
Keyword chronic kidney disease
genetics and development
vascular endothelial growth factor
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 15 times in Thomson Reuters Web of Science Article | Citations
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Created: Sun, 29 Nov 2009, 00:02:28 EST