Regular article
Vascular biology, atherosclerosis, and endothelium biology
ProxTom Lymphatic Vessel Reporter Mice Reveal Prox1 Expression in the Adrenal Medulla, Megakaryocytes, and Platelets

https://doi.org/10.1016/j.ajpath.2011.12.026Get rights and content
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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.

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L.A.T. was supported by Lymphoma Leukaemia Research 09018 and Brown-Coxe fellowships; K.L.B. was supported by Juvenile Diabetes Research Fund 44-2008-912. N.H.R.'s laboratory was supported by NIH DK 57331 and R21HL098711. D.J. was supported by a National Research Service Award, National Cancer Institute, Ruth Kirschstein Predoctoral Fellowship F31 CA 136316. W.M.'s laboratory was supported by NIH 2R01HL077357. E.C.S. was supported by National Research Service Award F31HLO94118. S.A.M. was supported by 109SCAYALE11 and NIH 5K12HD001401-09. D.S.K.'s laboratory was supported by NIH DK072442 (D.S.K.) and Connecticut grant 06SCB18. The two-photon microscope is part of the Yale Rheumatologic Diseases Core Center supported by NIH P30 AR053495.

L.A.T. and K.L.B. contributed equally to this work.

Supplemental material for this article can be found at http://ajp.amjpathol.org or at doi: 10.1016/j.ajpath.2011.12.026.