A modified mouse-tail lymphedema model

Abstract

One of the main obstacles to studying the pathophysiology of lymphedema development is the lack of appropriate experimental models. Fol-lowing up on a mouse-tail method that has been described, we performed changes to the method which made it easier to perform in our hands and demonstrated similar results. Twenty C57Black mice were operated on using the previous tech-nique and euthanized after 3 or 6 weeks. Another twenty mice were submitted to the new technique developed in our laboratory and euthanized at the same time points. Tissue samples were collected from the proximal part of the tail (control) and from the distal part (lymphedema) for both mod-els. Animals in both operative groups developed marked edema in the distal part of the tail. This was characterized by lymph vessels dilation, edema, inflammatory cell infiltration, and adipose tissue deposition. Lymphedema was detected after 3 weeks in both models, reaching its maximum after 6 weeks. Adipocytes detected by histology (Oil red O staining) and molecular markers for adipogenesis, lymphangiogenesis and inflam-mation (lipin 1 and 2, SLP76, and F4-80) were demonstrated to be increased equally in both models. In conclusion, both models provide a reliable method to study lymphedema pathophys-iology. However, our modified technique is easier and faster to perform while still providing reliable and consistent results.

Keywords: histology; lymphedema; molecular markers; mouse model; signaling pathways.