Pericyte-specific expression of PDGF beta receptor in mouse models with normal and deficient PDGF beta receptor signaling

Background: Pericytes are integral members of the neurovascular unit. Using mouse models lacking endothelial-secreted platelet derived growth factor-B (PDGF-B) or platelet derived growth factor receptor beta (PDGFR beta) on pericytes, it has been demonstrated that PDGF-B/PDGFR beta interactions mediate pericyte recruitment to the vessel wall in the embryonic brain regulating the development of the cerebral microcirculation and the blood-brain barrier (BBB). Relatively little is known, however, about the roles of PDGF-B/PDGFR beta interactions and pericytes in the adult brain in part due to a lack of adequate and/or properly characterized experimental models. To address whether genetic disruption of PDGFR beta signaling would result in a pericyte-specific insult in adult mice, we studied the pattern and cellular distribution of PDGFR beta expression in the brain in adult control mice and F7 mice that express two hypomorphic Pdgfr beta alleles containing seven point mutations in the cytoplasmic domain of PDGFR beta that impair downstream PDGFR beta receptor signaling. Results: Using dual fluorescent in situ hybridization, immunofluorescent staining for different cell types in the neurovascular unit, and a fluorescent in situ proximity ligation assay to visualize molecular PDGF-B/PDGFR beta interactions on brain tissue sections, we show for the first time that PDGFR beta is exclusively expressed in pericytes, and not in neurons, astrocytes or endothelial cells, in the adult brain of control 129S1/SvlmJ mice. PDGFR beta co-localized only with well-established pericyte markers such as Chondroitin Sulfate Proteoglycan NG2 and the xLacZ4 transgenic reporter. We next confirm pericyte-specific PDGFR beta expression in the brains of F7 mutants and show that these mice are viable in spite of substantial 40-60% reductions in regional pericyte coverage of brain capillaries. Conclusions: Our data show that PDGFR beta is exclusively expressed in pericytes in the adult 129S1/Sv1mJ and F7 mouse brain. Moreover, our findings suggest that genetic disruption of PDGFR beta signaling results in a pericyte-specific insult in adult F7 mutants and will not exert a primary effect on neurons because PDGFR beta is not expressed in neurons of the adult 129S1/SvlmJ and F7 mouse brain. Therefore, mouse models with normal and deficient PDGFR beta signaling on a 129S1/SvlmJ background may effectively be used to deduce the specific roles of pericytes in maintaining the cerebral microcirculation and BBB integrity in the adult and aging brain as well as during neurodegenerative and brain vascular disorders.