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Lack of lymphatic vessel phenotype in LYVE-1/CD44 double knockout mice

✍ Scribed by Mai X. Luong; Joshua Tam; Qingcong Lin; Jeroen Hagendoorn; Kathryn J. Moore; Timothy P. Padera; Brian Seed; Dai Fukumura; Raju Kucherlapati; Rakesh K. Jain


Publisher
John Wiley and Sons
Year
2009
Tongue
English
Weight
312 KB
Volume
219
Category
Article
ISSN
0021-9541

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✦ Synopsis


Abstract

Lymphatic vessels play a key role in maintaining tissue‐fluid homeostasis, immune surveillance and metastasis. The hyaluronan receptor, LYVE‐1, is widely used as a molecular marker for adult and embryonic lymphatic endothelium, but its physiological functions have not yet been established in vivo. In agreement with a recent report, LYVE‐1^−/−^ mice, which are healthy and fertile, do not display any defects related to congenital abnormalities of the lymphatic system. One hypothesis for the absence of a phenotype in LYVE‐1 null mice is that other hyaluronan receptors, such as CD44, may compensate for LYVE‐1. To test this hypothesis, we created LYVE‐1/CD44 double knockout mice with appropriate littermate controls. Lymphatic vessel structure and function, as determined by histological methods and intravital microscopy, show that LYVE‐1^−/−^, CD44^−/−^ and LYVE‐1^−/−^/CD44^−/−^ mice are indistinguishable from wild‐type mice under normal conditions. Furthermore, resolution of carrageenan‐induced paw edema is comparable in all genotypes. However, LYVE‐1^−/−^/CD44^−/−^ mice exhibit increased edema formation in a carrageenan‐induced paw inflammation model compared to wild‐type mice, but not to LYVE^−/−^ or CD44^−/−^ mice. These data suggest that LYVE‐1 and CD44 are not required for the formation or function of lymphatics, but do not rule out a role for LYVE‐1 in inflammation. J. Cell. Physiol. 219: 430–437, 2009. © 2009 Wiley‐Liss, Inc.