Visualization and characterization of rat lymphatic vasculature in a Prox1-EGFP bacterial artificial chromosome (BAC) transgenic rat: a novel animal model for physiological and pathological lymphangiogenesis

In the human body there are two fundamental circulatory networks, the blood and the lymphatic system, which are anatomically similar and complementary in function. Despite its significant role in drainage of excess interstitial fluid, transport of dietary lipids and execution of precise immune responses, the lymphatic vasculature was considered subordinate to the blood vasculature for many decades (Oliver 2004). Recent progresses in lymphatic research, such as the discovery of lymphatic-specific molecular markers (Banerji, Ni et al. 1999), lineage tracing of Prox1-expressing lymphatics (Srinivasan, Dillard et al. 2007), advancement of imaging techniques (Yaniv, Isogai et al. 2006), and development of various lymphatic-specific reporter mice have shown how the lymphatic vasculature plays an important role in the maintenance and enhancement of human health (Choi, Lee et al. 2012; Yang and Oliver 2014). Moreover, dysfunction in the lymphatic system can lead to multiple ailments such as lymphedema, obesity, chronic inflammation, autoimmunity, and metastasis, emphasizing a good mammalian lymphatic model to be essential in developing therapeutic drugs (Oliver 2004; Randolph, Angeli et al. 2005; Wang and Oliver 2010; Alitalo 2011; Choi, Lee et al. 2012; Weitman, Aschen et al. 2013; Stacker, Williams et al. 2014). Here, we report a bacterial artificial chromosome (BAC)-based transgenic rat that expresses GFP under the control of a Prox1 promoter. The GFP expression of the lymphatic vasculature was comprehensively investigated in various tissues and organs, demonstrating that the lymphatic vasculatures in the rats were visualized to even minute details. Our Prox1-EGFP rat implies enormous potential to be a powerful experimental tool for the better study of the lymphatic vasculature, both in developmental and pathological aspect.