Analysis of FSTL1 function in lymphatic development using conventional and endothelial cell-specific Fstl1 knockout mice

• 1、Cyrus Tang Hematology Center,Soochow University,Suzhou 215123

Abstract：Objection: To explore the biological function of FSTL1 in murine lymphatic network formation and maturation at embryonic and postnatal stages using knockout mouse models targeting Fstl1. Methods: This study employed three genetically modified mouse models, including a conditioned knockout mouse model targeting Fstl1 (Fstl1Flox/Flox), transgenic mice expressing Cre recombinase in vascular endothelial cells (Tie2-cre), and Fstl1 heterozygous mice (Fstl1+/-). Results: Previous study in our lab found that Fstl1ECKO/- mice could survive until birth, but most mice died at about 3 weeks due to abnormal vascular remodeling. To investigate whether FSTL1 deletion affects lymphatic formation and remodeling, lymphatic vessels of various tissues were analyzed at different stages after birth using fluorescent immunohistochemistry. Results showed that endothelial cell Fstl1 knockout had no significant effect on the formation of lymphatic capillary network, collecting lymphatic vessels and valve development. In order to further analyze whether FSTL1 from other cells has a compensatory effect on lymphatic development, we also generated full Fstl1 knockout mice(Fstl1-/-) . We showed that full FSTL1 deletion had no significant effect on lymphatic formation, maturation and remodeling of E18.5 mesentery lymphatic vessels. Conclusion: Studies using genetically modified mice have shown that FSTL1 is not necessary for lymphatic development, and its role in lymphatic formation at pathological conditions remains to be investigated.

Keywords： Follistain-like 1 (FSTL1) lymphatic capillaries collecting lymphatic vessel and valve lymphatic maturation and remodeling conditioned knockout mice