The effect of combined PDGF-B and PDGF-C deficiency on mouse development and brain vasculature

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In this project, we bred PDGF-B retention motif knockout (PDGF-Bret) mice with PDGF-C knockout mice to explore the effects of combined PDGF-B and PDGF-C deficiency on mouse development and brain vasculature. The PDGF-Bret/ret; PDGF-C-/- double knockout mice were born both dead and alive, but none survived weaning. While severe edema and hemorrhage were observed, no specific macroscopic malformations were noted. The brain vasculature in newborn PDGF-Bret/ret; PDGF-C-/- mice showed lower density and a more distorted architecture compared to controls, although significant changes could not be demonstrated. In adult mice, there were no significant differences in vascular density between PDGF-Bret/ret; PDGF-C+/- and PDGF-Bret/ret mice, but some regions exhibited significantly larger perimeter and length of vessels. Regarding mural cells, no significant changes in pericyte architecture were observed, but there was a suggested thicker vSMC coverage of larger vessels in PDGF-Bret/ret; PDGF-C+/- mice, consistent with findings in PDGF-C-/- mice. Overall, our data indicates that combined PDGF-B and PDGF-C deficiency allows normal embryonic development but limits survival post-birth, likely due to severe angiogenic system malfunctions. Our histopathologic analysis supports the role of PDGF-B and PDGF-C in the neurovascular unit, suggesting their interaction is not distinct enough for partial deficiency to cause extreme phenotypic changes.