The challenge
Obesity is known to affect many organs and is associated with inflammation, metabolic dysfunction and neurological complications. However, most available methods examine selected tissues rather than the entire body. This makes it difficult to understand how disease-related changes in nerves, immune cells and organs are connected across biological systems. Whole-body light-sheet microscopy can visualize large transparent samples, but analysing these massive three-dimensional datasets requires robust computational tools. Until now, there has been no scalable approach to quantify fine nerve structures, immune-cell clusters and tissue context across the full mouse body at cellular resolution.
Our approach
We developed MouseMapper, an AI-based analysis framework for cleared and light-sheet imaged mouse bodies. It combines modules for nerve segmentation, immune-cell detection and anatomical mapping of 31 organs and tissues, followed by spatial proteomics of selected disease-relevant regions.
Our findings
MouseMapper detected obesity-associated changes throughout the body. In obese mice, nerve density was reduced, especially in adipose tissue and the head. The infraorbital branch of the trigeminal nerve showed fewer endings and reduced network complexity, which was linked to impaired whisker sensing. Proteomic analysis of the trigeminal ganglion revealed changes in pathways related to axon guidance, cytoskeletal regulation and inflammation. Similar molecular signatures were also observed in human trigeminal ganglia from individuals with obesity.
The implications
MouseMapper provides a scalable way to study systemic disease in 3D. It may help identify disease hotspots and guide molecular analyses toward new therapeutic targets.
Creating SyNergies
The study brings together expertise in tissue clearing, whole-body imaging, deep learning, spatial proteomics and metabolic disease research linking advanced imaging technologies with systems neuroscience and translational disease biology to better understand how local cellular changes reflect whole-body pathology.
