RESUMO
The lymphatic system is essential in many physiological and pathological processes. Still, much remains to be known about the molecular mechanisms that control its development and function and how to modulate them therapeutically. The study of these mechanisms will benefit from better controlled genetic mouse models targeting specifically lymphatic endothelial cells. Among the genes expressed predominantly in lymphatic endothelium, Vegfr3 was the first one identified and is still considered to be one of the best lymphatic markers and a key regulator of the lymphatic system. Here, we report the generation of a Vegfr3-CreER (T2) knockin mouse by gene targeting in embryonic stem cells. This mouse expresses the tamoxifen-inducible CreER(T2) recombinase under the endogenous transcriptional control of the Vegfr3 gene without altering its physiological expression or regulation. The Vegfr3-CreER (T2) allele drives efficient recombination of floxed sequences upon tamoxifen administration specifically in Vegfr3-expressing cells, both in vitro, in primary lymphatic endothelial cells, and in vivo, at different stages of mouse embryonic development and postnatal life. Thus, our Vegfr3-CreER (T2) mouse constitutes a new powerful genetic tool for lineage tracing analysis and for conditional gene manipulation in the lymphatic endothelium that will contribute to improve our current understanding of this system.
Assuntos
Sistema Linfático/metabolismo , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/genética , Animais , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Introdução de Genes/métodos , Integrases/genética , Sistema Linfático/citologia , Sistema Linfático/crescimento & desenvolvimento , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Gravidez , Tamoxifeno/farmacologiaRESUMO
Atypical chemokine receptors (ACRs) are cell surface receptors with seven transmembrane domains structurally homologous to chemokine G-protein coupled receptors (GPCRs). However, upon ligation by cognate chemokines, ACRs fail to induce classical signaling and downstream cellular responses characteristic for GPCRs. Despite this, by affecting chemokine availability and function, ACRs impact on a multitude of pathophysiological events and have emerged as important molecular players in health and disease. This review discusses individual characteristics of the currently known ACRs, highlights their similarities and differences and attempts to establish their group identity. It summarizes the progress made in mapping ACR expression, understanding their diverse in vitro and in vivo functions of ACRs and uncovering their contributions to disease pathogeneses.
