Anuria, omphalocele, and perinatal lethality in mice lacking the CD34-related protein podocalyxin

Podocalyxin is a CD34-related sialomucin that is expressed at high levels b y podocytes, and also by mesothelial cells, vascular endothelia, platelets, and hematopoietic stem cells. To elucidate the function of podocalyxin, we generated podocalyxin-deficient (podxl(-/-)) mice by homologous recombinat ion. Null mice exhibit profound defects in kidney development and die with 24 hours of birth with anuric renal failure. Although podocytes are present in the glomeruli of the podxl(-/-) mice, they fail to form a foot processe s and slit diaphragms and instead exhibit cell-cell junctional complexes (t ight and adherens junctions). The corresponding reduction in permeable, glo merular filtration surface area presumably leads to the observed block in u rine production. In addition, podxl(-/-) mice frequently display herniation of the gut (omphalocele), suggesting that podocalyxin may be required for retraction of the gut from the umbilical cord during development. Hematopoi etic and vascular endothelial cells develop normally in the podocalyxin-def icient mice, possibly through functional compensation by other sialomucins (such as CD34). Our results provide the first example of an essential role for a sialomucin in development and suggest that defects in podocalyxin cou ld play a role in a podocyte dysfunction in renal failure and omphalocele i n humans.