| First Author | Shen B | Year | 2014 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 34 |
| Issue | 6 | Pages | 1221-30 |
| PubMed ID | 24764452 | Mgi Jnum | J:271100 |
| Mgi Id | MGI:6280405 | Doi | 10.1161/ATVBAHA.113.302923 |
| Citation | Shen B, et al. (2014) Genetic dissection of tie pathway in mouse lymphatic maturation and valve development. Arterioscler Thromb Vasc Biol 34(6):1221-30 |
| abstractText | OBJECTIVE: The genetic program underlying lymphatic development is still incompletely understood. This study aims to dissect the role of receptor tyrosine kinase with immunoglobulin-like and EGF (epidermal growth factor)-like domains 1 (Tie1) and Tie2 in lymphatic formation using genetically modified mouse models. APPROACH AND RESULTS: We generated conditional knockout mouse models targeting Tie1, Tie2, and angiopoietin-2 in this study. Tie1(DeltaICD/DeltaICD) mice, with its intracellular domain targeted, appeared normal at E10.5 but displayed subcutaneous edema by E13.5. Lymph sac formation occurred in Tie1(DeltaICD/DeltaICD) mice, but they had defects with the remodeling of primary lymphatic network to form collecting vessels and valvulogenesis. Consistently, induced deletion of Tie1-ICD postnatally using a ubiquitous Cre deleter led to abnormal lymphangiogenesis and valve formation in Tie1-ICD(iUCKO/-) mice. In comparison with the lymphatic phenotype of Tie1 mutants, we found that the diameter of lymphatic capillaries was significantly less in mice deficient of angiopoietin-2, besides the disruption of collecting lymphatic vessel formation as previously reported. There was also no lymphedema observed in Ang2(-/-) mice during embryonic development, which differs from that of Tie1(DeltaICD/DeltaICD) mice. We further investigated whether Tie1 exerted its function via Tie2 during lymphatic development. To our surprise, genetic deletion of Tie2 (Tie2(iUCKO/-)) in neonate mice did not affect lymphatic vessel growth and maturation. CONCLUSIONS: In contrast to the important role of Tie2 in the regulation of blood vascular development, Tie1 is crucial in the process of lymphatic remodeling and maturation, which is independent of Tie2. |
