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First published online March 30, 2004
doi: 10.1242/10.1242/dev.01080

Development 131, 1847-1857 (2004)
Published by The Company of Biologists 2004
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Endothelium-specific ablation of PDGFB leads to pericyte loss and glomerular, cardiac and placental abnormalities

Mattias Bjarnegård1, Maria Enge1, Jenny Norlin1, Sigrun Gustafsdottir2, Simon Fredriksson2, Alexandra Abramsson1, Minoru Takemoto1, Erika Gustafsson3, Reinhard Fässler4 and Christer Betsholtz1,*

1 Department of Medical Biochemistry, Göteborg University, PO Box 440, SE 405 30 Göteborg, Sweden
2 Department of Genetics and Pathology, Rudbeck Laboratory, SE 751 85 Uppsala, Sweden
3 Department of Experimental Pathology, Lund University, SE 221 85 Lund, Sweden
4 Max Planck Institute for Biochemistry, Department of Molecular Medicine, Am Klopferspitz 18a, D-82152 Martinsried, Germany

* Author for correspondence (e-mail: christer.betsholtz{at}medkem.gu.se)

Accepted 17 December 2003

Platelet-derived growth factor-B (PDGFB) is necessary for normal cardiovascular development, but the relative importance of different cellular sources of PDGFB has not been established. Using Cre-lox techniques, we show here that genetic ablation of Pdgfb in endothelial cells leads to impaired recruitment of pericytes to blood vessels. The endothelium-restricted Pdgfb knockout mutants also developed organ defects including cardiac, placental and renal abnormalities. These defects were similar to those observed in Pdgfb null mice. However, in marked contrast to the embryonic lethality of Pdgfb null mutants, the endothelium-specific mutants survived into adulthood with persistent pathological changes, including brain microhemorrhages, focal astrogliosis, and kidney glomerulus abnormalities. This spectrum of pathological changes is reminiscent of diabetic microangiopathy, suggesting that the endothelium-restricted Pdgfb knockouts may serve as models for some of the pathogenic events of vascular complications to diabetes.

Key words: PDGFB, Endothelium, Cre, loxP, Pericytes, Microaneurysm


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