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The Claudin-like protein of 24 kDa (CLP24) is a hypoxia-regulated transmembrane protein of unknown function. We show here that  clp24  knockdown in  Danio rerio  and  Xenopus laevis  results in defective lymphatic development. Targeted disruption of  Clp24  in mice led to enlarged lymphatic vessels having an abnormal smooth muscle cell coating. We also show that the  Clp24  −/−  phenotype was further aggravated in the  Vegfr2 +/LacZ   or  Vegfr3 +/LacZ   backgrounds and that CLP24 interacts with vascular endothelial growth factor receptor-2 (VEGFR-2) and VEGFR-3 and attenuates the transcription factor CREB phosphorylation via these receptors. Our results indicate that CLP24 is a novel regulator of VEGFR-2 and VEGFR-3 signaling pathways and of normal lymphatic vessel structure.

Claudin-like protein 24 interacts with the VEGFR-2 and VEGFR-3 pathways and regulates lymphatic vessel development