Lack of lymphatic vessel phenotype in LYVE-1/CD44 double knockout mice.
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.
Luong
Mai X
MX
Department of Radiation Oncology, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
Tam
Joshua
J
Lin
Qingcong
Q
Hagendoorn
Jeroen
J
Moore
Kathryn J
KJ
Padera
Timothy P
TP
Seed
Brian
B
Fukumura
Dai
D
Kucherlapati
Raju
R
Jain
Rakesh K
RK
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
D006023:Glycoproteins; D018960:Hyaluronan Receptors; D026901:Membrane Transport Proteins; C476399:Cd44 protein, mouse; C492273:LYVE1 protein, mouse