title: Lack of lymphatic vessel phenotype in LYVE-1/CD44 double knockout mice.
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.
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
authors.forename: Mai X
authors.initials: MX
authors.lastname: Luong
authors.forename: Joshua
authors.initials: J
authors.lastname: Tam
authors.forename: Qingcong
authors.initials: Q
authors.lastname: Lin
authors.forename: Jeroen
authors.initials: J
authors.lastname: Hagendoorn
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Moore
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Padera
authors.forename: Brian
authors.initials: B
authors.lastname: Seed
authors.forename: Dai
authors.initials: D
authors.lastname: Fukumura
authors.forename: Raju
authors.initials: R
authors.lastname: Kucherlapati
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Jain
mesh_terms: D000818:Animals; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology; D005260:Female; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D042601:Lymphatic Vessels / Q000033:anatomy & histology / Q000502:physiology; D008297:Male; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype
chemical_list: D006023:Glycoproteins; D018960:Hyaluronan Receptors; D026901:Membrane Transport Proteins; C476399:Cd44 protein, mouse; C492273:LYVE1 protein, mouse