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Endothelium-specific ablation of PDGFB leads to pericyte loss and glomerular, cardiac and placental abnormalities

Bjarnegard, M; Enge, M; Norlin, J; Gustafsdottir, S; Fredriksson, S; Abramsson, A; Takemoto, M; Gustafsson, Erika LU ; Fassler, R and Betsholtz, C (2004) In Development 131(8). p.1847-1857
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
PDGFB, Cre, loxP, microaneurysm, pericytes, endothelium
in
Development
volume
131
issue
8
pages
1847 - 1857
publisher
Society for International Development
external identifiers
  • pmid:15084468
  • wos:000221155900016
  • scopus:2342431290
ISSN
1477-9129
DOI
10.1242/10.1242/dev.01080
language
English
LU publication?
yes
id
306946ab-ca7e-4acf-86a1-746cc66f3a86 (old id 279925)
date added to LUP
2007-10-17 09:43:19
date last changed
2017-12-17 03:27:57
@article{306946ab-ca7e-4acf-86a1-746cc66f3a86,
  abstract     = {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.},
  author       = {Bjarnegard, M and Enge, M and Norlin, J and Gustafsdottir, S and Fredriksson, S and Abramsson, A and Takemoto, M and Gustafsson, Erika and Fassler, R and Betsholtz, C},
  issn         = {1477-9129},
  keyword      = {PDGFB,Cre,loxP,microaneurysm,pericytes,endothelium},
  language     = {eng},
  number       = {8},
  pages        = {1847--1857},
  publisher    = {Society for International Development},
  series       = {Development},
  title        = {Endothelium-specific ablation of PDGFB leads to pericyte loss and glomerular, cardiac and placental abnormalities},
  url          = {http://dx.doi.org/10.1242/10.1242/dev.01080},
  volume       = {131},
  year         = {2004},
}