A new Mmrn1-CreERT2 Mouse Model for High-Fidelity Labeling of Adult Lymphatic Endothelium

Abstract

Cell type-specific Cre driver lines are essential for studying organ-specific biology in vivo, but recombination in unintended targets can limit their interpretive power. The dural meninges harbor a distinct network of lymphatic vessels implicated in neurological processes ranging from neurodevelopment to neurodegeneration. Current lymphatic reporters, driven by Prox1, Lyve1 or Vegfr3, efficiently recombine in lymphatic endothelial cells, including in the dura, but are also expressed in other CNS cell populations, resulting in non-lymphatic recombination that complicates interpretation. Here, we identify Mmrn1 as a gene specifically enriched in lymphatic endothelial cells throughout the body, with no detectable expression in other CNS cells. We generated an Mmrn1CreERT2 mouse line and show that, in adult mice, it drives recombination restricted to lymphatic endothelial cells, with no detectable recombination in non-lymphatic CNS populations. A similar but less complete recombination is observed in developing mice. This tool offers the lymphatic field a new means to specifically manipulate lymphatic vasculature and study its cell-specific functions.