Endothelium-specific ablation of PDGFB leads to pericyte loss and glomerular, cardiac and placental abnormalities.
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.
Bjarnegård
Mattias
M
Department of Medical Biochemistry, Göteborg University, PO Box 440, SE 405 30 Göteborg, Sweden.
Enge
Maria
M
Norlin
Jenny
J
Gustafsdottir
Sigrun
S
Fredriksson
Simon
S
Abramsson
Alexandra
A
Takemoto
Minoru
M
Gustafsson
Erika
E
Fässler
Reinhard
R
Betsholtz
Christer
C
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D001921:Brain / Q000098:blood supply; D004727:Endothelium / Q000378:metabolism; D006330:Heart Defects, Congenital / Q000235:genetics / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000002:abnormalities / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D020286:Pericytes / Q000378:metabolism*; D010920:Placenta / Q000002:abnormalities / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000378:metabolism*; D042810:Receptor, TIE-1 / Q000235:genetics / Q000378:metabolism
D020574:Proto-Oncogene Proteins c-sis; D042810:Receptor, TIE-1