Viability of transgenic mice expressing a platelet derived growth factor (PDGF) antagonist in plasma.
BACKGROUND
Many studies have implicated PDGF in the development of diseases such as atherosclerosis. Previously, we showed in tissue culture that the soluble extracellular domain of the PDGF beta-receptor is capable of binding BB-PDGF with high affinity; therefore antagonizing the ability of BB-PDGF to stimulate cell growth.


METHODS
This work describes the efforts of expressing the soluble extracellular domain of the PDGF beta-receptor in transgenic mice. Driven by the albumin promoter, which is activated relatively late during embryonic development, the secreted form of the PDGF receptor protein was detected in plasma of the homozygous mice at a high concentration (approximately 60 micrograms/microL or approximately 545 nm).


RESULTS
Plasma from these transgenic mice was capable of blocking PDGF-induced receptor autophosphorylation in tissue culture. The mice appeared to be healthy, demonstrating that full PDGF beta-receptor function is not required for viability.


CONCLUSIONS
By expressing a high level of a soluble form of the extracellular domain of the PDGF receptor in transgenic mice, we have established a novel animal model that will allow us to gain insight into the role of the PDGF receptor in vascular diseases and other diseases involving PDGF stimulated cell proliferation.
Liao
X
X
Daiichi Research Center, Cardiovascular Research Institute, San Francisco, CA, USA.
Escobedo
J A
JA
Williams
L T
LT
D000818:Animals; D001161:Arteriosclerosis / Q000097:blood; D000077214:Becaplermin; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006720:Homozygote; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics*
D018076:DNA, Complementary; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor