Pericytes are essential mural cells distinguished by their association with small caliber vessels and the presence of a basement membrane shared with endothelial cells. Pericyte interaction with the endothelium plays an important role in angiogenesis, however very few tools are currently available that allow for the targeting of pericytes in mouse models, limiting our ability to understand their biology. We have generated a novel mouse line expressing tamoxifen-inducible Cre-recombinase under the control of the platelet derived growth factor receptor β promoter: PDGFRβ-P2A-CreERT2. We evaluated the expression of the PDGFRβ-P2A-CreERT2 line by crossing it with fluorescent reporter lines and analyzed reporter signal in the angiogenic retina and brain at different time points after tamoxifen administration. Reporter lines showed labeling of NG2+, desmin+, PDGFRβ+ perivascular cells in the retina and the brain, indicating successful targeting of pericytes; however, signal from reporter lines was also observed in a small subset of glial cells both in the retina and the brain. We also evaluated recombination in tumors and found efficient recombination in perivascular cells associated with tumor vasculature. As a proof of principle, we used our newly generated driver to delete Notch signaling in perivascular cells and observed a loss of smooth muscle cells in retinal arteries, consistent with previously published studies evaluating Notch3 null mice. We conclude that the PDGFRβ-P2A-CreERT2 line is a powerful new tool to target pericytes and will aid the field in gaining a deeper understanding of the role of these cells in physiological and pathological settings.

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Germinal matrix-intraventricular hemorrhage (GM-IVH) is the most devastating neurological complication in premature infants. GM-IVH usually begins in the GM, a highly vascularized region of the developing brain where glial and neuronal precursors reside underneath the lateral ventricular ependyma. Previous studies using human fetal tissue have suggested increased angiogenesis and paucity of pericytes as key factors contributing to GM-IVH pathogenesis. Yet, despite its relevance, the mechanisms underlying the GM vasculature's susceptibility to hemorrhage remain poorly understood. To gain better understanding on the vascular dynamics of the GM, we performed a comprehensive analysis of the mouse GM vascular endothelium and pericytes during development. We hypothesize that vascular development of the mouse GM will provide a good model for studies of human GM vascularization and provide insights into the role of pericytes in GM-IVH pathogenesis. Our findings show that the mouse GM presents significantly greater vascular area and vascular branching compared to the developing cortex (CTX). Analysis of pericyte coverage showed abundance in PDGFRβpositive and NG2-positive pericyte coverage in the GM similar to the developing CTX. However, we found a paucity in Desmin-positive pericyte coverage of the GM vasculature. Our results underscore the highly angiogenic nature of the GM and reveal that pericytes in the developing mouse GM exhibit distinct phenotypical and likely functional characteristics compared to other brain regions which might contribute to the high susceptibility of the GM vasculature to hemorrhage.

The purpose of this research is to provide a solution to regulate environmental diseases when the spread of the disease is partly based on how susceptible different groups of individuals are. This study will monitor the effects a disease has on a population with groups of different susceptibility through the administration of vaccines: a point vaccination scheme (PVS) and an interval vaccination scheme (IVS). A PVS entails the instantaneous vaccination of individuals by selectively distributing vaccinations at one point in time, while an IVS is a more realistic vaccination method administered over an interval of time. Both schemes are exclusively administered to individuals classified as having the highest susceptibility to disease. The disease itself will be explored through the use of an model of susceptibility classes, a model which studies a disease in relation to susceptible, infected, and removed individuals.To further study the disease, this same model will be modified through the incorporation of differential delay equations, denoting a regaining of susceptibility. These incorporations surface as a reflection of reality: in several diseases, it has been observed that vaccinated individuals or individuals with immunity to the original strain of a disease can regain susceptibility to a mutated strain, such as the common flu whose strains undergo constant mutation. Modification of the disease allows for recovering individuals to contract a viral variant.