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Viability of transgenic mice expressing a platelet derived growth factor (PDGF) antagonist in plasma
X Liao1, J A Escobedo, L T Williams
1Daiichi Research Center, Cardiovascular Research Institute, San Francisco, CA, USA.
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.
Conclusion:
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.
Insights
Researchers created transgenic mice expressing a soluble PDGF beta-receptor to study its role in diseases. The mice
Area of Science:
- Vascular Biology
- Receptor Signaling
- Transgenic Animal Models
Background:
- Platelet-derived growth factor (PDGF) is implicated in diseases like atherosclerosis.
- The soluble extracellular domain of the PDGF beta-receptor binds BB-PDGF, inhibiting cell growth.
- Previous studies demonstrated high-affinity binding of BB-PDGF by the soluble PDGF beta-receptor extracellular domain in vitro.
Purpose of the Study:
- To establish a transgenic mouse model expressing the soluble extracellular domain of the PDGF beta-receptor.
- To investigate the in vivo role of PDGF signaling in disease development.
- To create a tool for studying PDGF-mediated cellular processes.
Main Methods:
- Generation of transgenic mice using the albumin promoter to drive expression of the soluble PDGF beta-receptor extracellular domain.
- Quantification of secreted PDGF receptor protein in plasma of homozygous transgenic mice.
- Assessment of the functional capacity of plasma from transgenic mice to block PDGF signaling.
Main Results:
- High concentrations of soluble PDGF receptor protein were detected in the plasma of homozygous transgenic mice.
- Plasma from these mice effectively blocked PDGF-induced receptor autophosphorylation in vitro.
- Transgenic mice exhibited normal health, indicating PDGF beta-receptor function is not essential for viability.
Conclusions:
- A novel transgenic mouse model expressing high levels of soluble PDGF receptor was successfully developed.
- This model provides a valuable tool for elucidating the role of PDGF signaling in vascular diseases.
- The model can be utilized to study other conditions involving PDGF-stimulated cell proliferation.