Project 1 aims to develop a mouse model of vascular pathologies of systemic autoimmune diseases, especially in the central nervous system. The project is conducted by the Institute of Experimental and Clinical Pharmacology and Toxicology and includes mechanistic studies in vitro and in mice to decipher the action of the AT1R-AAB on brain endothelial cells. Support from P2 is essential for the immunization of mice, support from P3 is necessary to identify target organs of the AT1R-AAB, and support from P4 is critical to optimize in vivo microscopy using a two-photon microscope in SAIL. The overall aim of P1 is to provide a small animal platform for future behavioral and neurovascular investigations of autoantibody-mediated diseases. Within this project, we will use highly sophisticated microscopy techniques (white light laser confocal microscopy; STED) which enables microscopy below the optical resolution and will be used to identify and describe antibody binding patterns. We will start with the brain vasculature but dependent on the findings of P3, we will examine other tissues of interest as well.