Disease models

Mice with bone-specific overexpression of VEGF-C could be used to screen therapies to treat Gorham-Stout disease. Generation of the model involves crossing a mouse line, in which expression of a tetracycline transactivator cassette is controlled by Sp7 transcription factor (SP7), with a mouse line that has a targeted insertion of tet operator sequences in the VEGF-C promoter region, and treating the pregnant dams with doxycycline. The resulting offspring recapitulate the formation of lymphatic vessels in bone observed with Gorham-Stout disease. In the model, a tool compound vascular endothelial growth factor receptor 3 (FLT4; VEGFR-3) inhibitor decreased lymphatic vessel index score -- a marker of disease severity -- compared with vehicle. Also in the model, zoledronic acid decreased femur osteoclast number and porosity. Next steps could include using the model to screen additional therapies...