An inducible Cldn11-CreERT2 mouse line for selective targeting of lymphatic valves

Genesis. 2021 Aug;59(7-8):e23439. doi: 10.1002/dvg.23439. Epub 2021 Aug 2.


Luminal valves of collecting lymphatic vessels are critical for maintaining unidirectional flow of lymph and their dysfunction underlies several forms of primary lymphedema. Here, we report on the generation of a transgenic mouse expressing the tamoxifen inducible CreERT2 under the control of Cldn11 promoter that allows, for the first time, selective and temporally controlled targeting of lymphatic valve endothelial cells. We show that within the vasculature CLDN11 is specifically expressed in lymphatic valves but is not required for their development as mice with a global loss of Cldn11 display normal valves in the mesentery. Tamoxifen treated Cldn11-CreERT2 mice also carrying a fluorescent Cre-reporter displayed reporter protein expression selectively in lymphatic valves and, to a lower degree, in venous valves. Analysis of developing vasculature further showed that Cldn11-CreERT2 -mediated recombination is induced during valve leaflet formation, and efficient labeling of valve endothelial cells was observed in mature valves. The Cldn11-CreERT2 mouse thus provides a valuable tool for functional studies of valves.

Keywords: Cre recombinase; lymphatic vessel; valve.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Claudins / genetics*
  • Claudins / metabolism
  • Gene Targeting / methods*
  • Integrases / genetics
  • Integrases / metabolism
  • Lymphatic Vessels / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Promoter Regions, Genetic
  • Tamoxifen / pharmacology
  • Transcriptional Activation / drug effects
  • Transgenes


  • Claudins
  • Cldn11 protein, mouse
  • Tamoxifen
  • Cre recombinase
  • Integrases