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

In this project we bred together PDGF-B retention motif knockout (PDGF- Bret) mice and PDGF-C knockout mice for the first time to investigate the effect of combined PDGF-B and PDGF-C deficiency on mouse development and brain vasculature. PDGF-Bret/ret;PDGF-C-/- double knockout mice were born dead and alive, but none survived weaning. Though severe oedema and haemorrhage was observed, they did not show any specific macroscopic malformation. The brain vasculature of new born (P0) PDGF-Bret/ret;PDGF-C-/- double knockout mice seemed to present a lower density and a more distorted architecture compared to PDGF-Bret/ret;PDGF-C+/-,PDGF-Bret/ret mice, but no significant changes could be shown. Comparing the brain vasculature of adult PDGF-Bret/ret;PDGF-C+/- and PDGF-Bret/ret mice we could not show significant differences of vascular density, but we were able to detect significant higher perimeter and length of the vessels in some parts of the brain. Looking at mural cells we could not show significant changes in pericyte architecture, but our observations suggest a thicker vSMC coverage of big vessels in PDGF-Bret/ret;PDGF-C+/- mice, an effect already described in PDGF-C-/-mice (Fredriksson et al., 2012). In conclusion, our data suggests that combined PDGF-B and PDGF-C deficiency in mice allows a normal macroscopic embryonic development, but limits surviving after birth presumably also due to severe malfunctions of the angiogenic system. Our histopathologic analysis of the brain vasculature underlines the described effect of PDGF-B and PDGF-C on the neurovascular unit, but suggests that the interaction and redundancy of these two PDGFs is not sufficiently distinct for a partial deficiency leading to extreme phenotypic changes.