
<ArticleTitle>Anuria, omphalocele, and perinatal lethality in mice lacking the <prot>CD34</prot>-related protein <prot>podocalyxin</prot>.</ArticleTitle>
<AbstractText><prot>Podocalyxin</prot> is a <prot><prot>CD34</prot>-related sialomucin</prot> that is expressed at high levels by podocytes, and also by mesothelial cells, vascular endothelia, platelets, and hematopoietic stem cells. To elucidate the function of <prot>podocalyxin</prot>, we generated <prot>podocalyxin</prot>-deficient (<prot>podxl</prot>(-/)-) mice by homologous recombination. Null mice exhibit profound defects in kidney development and die within 24 hours of birth with anuric renal failure. Although podocytes are present in the glomeruli of the <prot>podxl</prot>(-/)- mice, they fail to form foot processes and slit diaphragms and instead exhibit cell--cell junctional complexes (tight and adherens junctions). The corresponding reduction in permeable, glomerular filtration surface area presumably leads to the observed block in urine production. In addition, <prot>podxl</prot>(-/)- mice frequently display herniation of the gut (omphalocele), suggesting that <prot>podocalyxin</prot> may be required for retraction of the gut from the umbilical cord during development. Hematopoietic and vascular endothelial cells develop normally in the <prot>podocalyxin</prot>-deficient mice, possibly through functional compensation by other sialomucins (such as <prot>CD34</prot>). Our results provide the first example of an essential role for a sialomucin in development and suggest that defects in <prot>podocalyxin</prot> could play a role in podocyte dysfunction in renal failure and omphalocele in humans.</AbstractText>
