ABSTRACT Most diseases involve multiple interconnected physiological systems, but histological evaluation of their pathology is currently limited to small tissue samples. Here, we present wildDISCO, a technology that uses cholesterol extraction to enable deep tissue penetration of standard 150 kDa IgG antibodies in chemically fixed whole mice. Combining wildDISCO with whole mouse clearing, we generate whole-body maps of the nervous, immune, and lymphatic systems and show their close interactions throughout the mouse body. Graphical Abstract Highlights WildDISCO uses new tissue chemistry based on β-cyclodextrin to enable histology in whole mouse bodies using full-size antibodies WildDISCO generates the first whole mouse body atlases for neurons, immune cells, blood and lymph vessels The whole mouse atlases are available online to study the biological systems in health and disease Virtual Reality (VR) exploration of these atlases disentangles complex anatomical structures between organs and biological systems Supplementary Videos can be seen at http://discotechnologies.org/wildDISCO/
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