| First Author | Winkler EA | Year | 2010 |
| Journal | Mol Neurodegener | Volume | 5 |
| Pages | 32 | PubMed ID | 20738866 |
| Mgi Jnum | J:244579 | Mgi Id | MGI:5913358 |
| Doi | 10.1186/1750-1326-5-32 | Citation | Winkler EA, et al. (2010) Pericyte-specific expression of PDGF beta receptor in mouse models with normal and deficient PDGF beta receptor signaling. Mol Neurodegener 5:32 |
| abstractText | 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 (PDGFRbeta) on pericytes, it has been demonstrated that PDGF-B/PDGFRbeta 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/PDGFRbeta 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 PDGFRbeta signaling would result in a pericyte-specific insult in adult mice, we studied the pattern and cellular distribution of PDGFRbeta expression in the brain in adult control mice and F7 mice that express two hypomorphic Pdgfrbeta alleles containing seven point mutations in the cytoplasmic domain of PDGFRbeta that impair downstream PDGFRbeta 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/PDGFRbeta interactions on brain tissue sections, we show for the first time that PDGFRbeta is exclusively expressed in pericytes, and not in neurons, astrocytes or endothelial cells, in the adult brain of control 129S1/SvlmJ mice. PDGFRbeta co-localized only with well-established pericyte markers such as Chondroitin Sulfate Proteoglycan NG2 and the xLacZ4 transgenic reporter. We next confirm pericyte-specific PDGFRbeta 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 PDGFRbeta is exclusively expressed in pericytes in the adult 129S1/Sv1mJ and F7 mouse brain. Moreover, our findings suggest that genetic disruption of PDGFRbeta signaling results in a pericyte-specific insult in adult F7 mutants and will not exert a primary effect on neurons because PDGFRbeta is not expressed in neurons of the adult 129S1/SvlmJ and F7 mouse brain. Therefore, mouse models with normal and deficient PDGFRbeta 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. |
