Beschreibung:
<jats:p>The Angiopoietin-Tie2 signaling pathway is a critical regulator in vascular development, with conventional Ang1 or Tie2 knockout mice dying in utero with vascular defects. While the role of this pathway in vascular development is apparent, the severity of developmental phenotypes makes it difficult to study Tie2 in vivo. Here, we investigate the functional role of Tie2 in embryonic as well as adult mice using inducible knockout mouse models (Tie2 cKO).</jats:p>
<jats:p>Tie2 inactivation at early stages of gestation (E12.5 or E14.5), which coincides with the initial stages of lymphatic development and remodeling, resulted in severe subcutaneous edema in E16.5 and altered lymphatic vessel morphology in the dermis of E17.5. These results indicate the important role of Tie2 in lymphatic development. In contrast, Tie2 inactivation at later stages (E18.5-P0) resulted in the birth of viable pups, indicating that Tie2 is dispensable after embryonic development. Adult male Tie2 cKO mice have similar blood glucose, glucose tolerance, and plasma lipids compared to controls. However, body weight of Tie2 cKO mice upon high-fat diet feeding was lower than that of control mice (47.5+-0.6g (control) vs. 38.0+-2.0g (Tie2 cKO), p<0.01 (4weeks after high-fat diet feeding)). Although plasma lipids (cholesterol and triglyceride) in control and Tie2 cKO mice were similar after high-fat diet feeding, mRNA expression of TNFa (100+-14% (control) vs. 40+-1.4% (Tie2 cKO), p<0.05) and F4/80 (100+-13% (control) vs. 53+-7.3% (Tie2 cKO), p<0.05) in epididymal fat were reduced in Tie2 cKO mice.</jats:p>
<jats:p>Our data show that Tie2 plays an import role in lymphatic development during embryogenesis and that Tie2 signaling is also important for adipose tissue growth in adult mice.</jats:p>