A novel, transgenic, inducible murine model of scrotal lymphedema
Jason C. Gardenier, MD, Jung-Ju Huang, MD, Ira Savetsky, MD, Geoffrey Hespe, BS, Gabriela Garcia Nores, MD, Catherine Ly, MD, Raghu Kataru, PhD, Babak Mehrara, MD.
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
BACKGROUND: Scrotal lymphedema is an extremely challenging clinical problem and is epidemic on a global level affecting an estimated 29 million men worldwide. Current treatments are radical and deforming and for this reasons many affected patients do not undergo treatment. There has been little research on this topic because an animal model of the disease has not previously existed. We describe the first animal model of scrotal lymphedema ever reported in the literature.
METHODS: We created Cre-lox mice that express the human diphtheria toxin receptor selectively on lymphatic endothelial cells (LECs) using a lymphatic specific promoter (FLT-4). This receptor binds diphtheria toxin (DT) avidly and allows selective ablation of the target cells. We injected DT in the scrotum to locally ablate scrotal lymphatics.
RESULTS: Over the course of one week, scrotal volumes increased to 520% of normal, and this volume increase was sustained for at least 4 weeks. Immunofluorescent staining for lymphatic vessels showed that there was a 66% reduction in dermal capillary lymphatic vessel density (p=0.003) and an 88% reduction in collecting lymphatic vessels (p<0.001). There was a 70% increase in T cell soft tissue infiltration (p=0.038), but no difference in macrophage soft tissue infiltration. There was also a 80% increase in epidermal thickness (p<0.001), representing hyperkeratosis.
CONCLUSIONS: We have created and described the first transgenic, inducible animal model of scrotal lymphedema. Further experiments with this model may allow for new discoveries of scrotal lymphatic function/dysfunction and will allow for the testing of surgical and pharmacological treatment possibilities.
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