ProxTom lymphatic vessel reporter mice reveal Prox1 expression in the adrenal medulla, megakaryocytes, and platelets.
Lymphatic vessels (LVs) are important structures for antigen presentation, for lipid metabolism, and as conduits for tumor metastases, but they have been difficult to visualize in vivo. Prox1 is a transcription factor that is necessary for lymphangiogenesis in ontogeny and the maintenance of LVs. To visualize LVs in the lymph node of a living mouse in real time, we made the ProxTom transgenic mouse in a C57BL/6 background using red fluorescent LVs that are suitable for in vivo imaging. The ProxTom transgene contained all Prox1 regulatory sequences and was faithfully expressed in LVs coincident with endogenous Prox1 expression. The progenies of a ProxTom × Hec6stGFP cross were imaged using two-photon laser scanning microscopy, allowing the simultaneous visualization of LVs and high endothelial venules in a lymph node of a living mouse for the first time. We confirmed the expression of Prox1 in the adult liver, lens, and dentate gyrus. These intensely fluorescent mice revealed the expression of Prox1 in three novel sites: the neuroendocrine cells of the adrenal medulla, megakaryocytes, and platelets. The novel sites identified herein suggest previously unknown roles for Prox1. The faithful expression of the fluorescent reporter in ProxTom LVs indicates that these mice have potential utility in the study of diseases as diverse as lymphedema, filariasis, transplant rejection, obesity, and tumor metastasis.
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06511, USA.
Lucy A
LA
Truman
Kevin L
KL
Bentley
Elenoe C
EC
Smith
Stephanie A
SA
Massaro
David G
DG
Gonzalez
Ann M
AM
Haberman
Myriam
M
Hill
Dennis
D
Jones
Wang
W
Min
Diane S
DS
Krause
Nancy H
NH
Ruddle
D000313:Adrenal Medulla / Q000378:metabolism*; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D005838:Genotype; D006023:Glycoproteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008164:Luminescent Proteins / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D042601:Lymphatic Vessels / Q000378:metabolism*; D008533:Megakaryocytes / Q000378:metabolism*; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D000097573:Red Fluorescent Protein; D000098551:Prospero-Related Homeobox 1 Protein
D006023:Glycoproteins; D018398:Homeodomain Proteins; D008164:Luminescent Proteins; D026901:Membrane Transport Proteins; D025521:Tumor Suppressor Proteins; D000097573:Red Fluorescent Protein; D000098551:Prospero-Related Homeobox 1 Protein; C492273:LYVE1 protein, mouse