Organ-specific lymphatics are essential for the maintenance of healthy organ function
and lymphatic dysfunction can lead to the development of various diseases. However,
the precise role of those lymphatic structures remains unknown, mainly due to inefficient
visualization techniques. Here, we present an efficient approach to visualizing organ-specific
lymphatic growth. We used a modified CUBIC protocol to clear mouse organs and combined
it with whole-mount immunostaining to visualize lymphatic structures. We acquired
images using upright, stereo and confocal microscopy and quantified them with AngioTool,
a tool for the quantification of vascular networks. Using our approach, we then characterized
the organ-specific lymphatic vasculature of the Flt4kd/+ mouse model, showing symptoms
of lymphatic dysfunction. Our approach enabled us to visualize the lymphatic vasculature
of organs and to analyze and quantify structural changes. We detected morphologically
altered lymphatic vessels in all investigated organs of Flt4kd/+ mice, including the
lungs, small intestine, heart and uterus, but no lymphatic structures in the skin.
Quantifications showed that these mice have fewer and dilated lymphatic vessels in
the small intestine and the lungs. Our results demonstrate that our approach can be
used to investigate the importance of organ-specific lymphatics under both physiological
and pathophysiological conditions.