ROBO4 (roundabout guidance receptor 4),also know as AOVD3, ECSM4, MRB(magic roundabout ), is a 107kD single chain type I membrane protein, which belongs to the immunoglobulin superfamily or ROBO family. ROBO4 contains 2 fibronectin type-III domains and 2 Ig-like C2-type (immunoglobulin-like) domains. It is specifically expressed in endothelial cells and at sites of angiogenesis in different tumor types. It can act as receptor for Slit proteins, at least for SLIT2, and seems to be involved in angiogenesis and vascular patterning. It may mediate the inhibition of primary endothelial cell migration by Slit proteins. Homozygous knockout leads to enhanced VEGF-induced endothelial migration, tube formation and vascular permeability, and increased pathologic angiogenesis and vascular leak in models of oxygen-induced retinopathy and choroidal neovascularization. Homozygous KO also improves glucose metabolism and adipose tissue angiogenesis when fed high-fat diet and increases exercise endurance on normal chow. The humanized monoclonal agonistic antibody DS-7080 developed by Daiichi SANKYO is now under phase I clinical trials.
The exons 1-9 of mouse Robo4 gene that encode the extracellular domain were replaced by human ROBO4 exons 1-9 in B-hROBO4 mice.
Protein expression analysis
Strain specific ROBO4 expression analysis in homozygous B-hROBO4 mice by western blot. Lung tissues were collected from wild-type C57BL/6 mice (+/+) and homozygous B-hROBO4 mice (H/H), and analyzed by western blot with anti-ROBO4 antibody. Human ROBO4 was exclusively detectable in homozygous B-hROBO4 mice.