Comparative analysis of lymphatic formation and remodeling in different tissues of mice with VEGFR-3 loss-of-function point mutation

• 1、Cyrus Tang Hematology Center,Soochow University,Suzhou 215123
• 2、CAM-SU Genomic Resource Center,Soochow University,Suzhou,215123

Abstract：To investigate the effect of VEGFR-3 mediated signals on postnatal lymphatic formation and remodeling in different tissues. Method: It was found in our previous study that mice homozygous for VEGFR-3 inactivation point mutation in its kinase region (Vegfr3TKmut/TKmut) displayed embryonic lethality before birth, and heterozygous mutant mice (Vegfr3WT/TKmut) had defective lymphatic development due to the dominant negative effect of VEGFR3TKmut. In this study, using whole-mount immunofluorescence technique, we compared lymphatic vessel growth in different tissues including skin, diaphragm，trachea of wildtype and mutant mice at different postnatal stages. Results: Vegfr3WT/TKmut mice showed significantly decreased postnatal survival rate compared to its littermate controls. There was a significant decrease of lymphatic density in skin but the diameter of lymphatic vessels became thicker in Vegfr3WT/TKmut mice. Interestingly, there was some level of lymphatic regrowth in the diaphragm of VEGFR-3 mutant mice, and these mice did not have chylous ascites by the week 3 stage. The distinct lymphatic abnormality was also observed in trachea of Vegfr3WT/TKmut mice where some mutant mice showed normal or weak lymphatic phenotype. Conclusion: It appears that there may be differential requirement of VEGFR-3 mediated signals for lymphangiogenesis among tissues. The cellular and molecular mechanism underlying the difference is still be to be investigated.

Keywords： VEGFR-3, receptor tyrosine kinase, lymphatic vessel, genetically modified mutant mice.