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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 by 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 recombina...

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Autores principales: Doyonnas, Regis, Kershaw, David B., Duhme, Christian, Merkens, Helen, Chelliah, Shierley, Graf, Thomas, McNagny, Kelly M.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2001
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193439/
https://www.ncbi.nlm.nih.gov/pubmed/11435469
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author Doyonnas, Regis
Kershaw, David B.
Duhme, Christian
Merkens, Helen
Chelliah, Shierley
Graf, Thomas
McNagny, Kelly M.
author_facet Doyonnas, Regis
Kershaw, David B.
Duhme, Christian
Merkens, Helen
Chelliah, Shierley
Graf, Thomas
McNagny, Kelly M.
author_sort Doyonnas, Regis
collection PubMed
description Podocalyxin is a CD34-related sialomucin 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 podocalyxin, we generated podocalyxin-deficient (podxl (−/)−) 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 podxl (−/)− 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, 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. Hematopoietic and vascular endothelial cells develop normally in the podocalyxin-deficient 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 could play a role in podocyte dysfunction in renal failure and omphalocele in humans.
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spelling pubmed-21934392008-04-14 Anuria, Omphalocele, and Perinatal Lethality in Mice Lacking the Cd34-Related Protein Podocalyxin Doyonnas, Regis Kershaw, David B. Duhme, Christian Merkens, Helen Chelliah, Shierley Graf, Thomas McNagny, Kelly M. J Exp Med Original Article Podocalyxin is a CD34-related sialomucin 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 podocalyxin, we generated podocalyxin-deficient (podxl (−/)−) 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 podxl (−/)− 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, 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. Hematopoietic and vascular endothelial cells develop normally in the podocalyxin-deficient 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 could play a role in podocyte dysfunction in renal failure and omphalocele in humans. The Rockefeller University Press 2001-07-02 /pmc/articles/PMC2193439/ /pubmed/11435469 Text en © 2001 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Original Article
Doyonnas, Regis
Kershaw, David B.
Duhme, Christian
Merkens, Helen
Chelliah, Shierley
Graf, Thomas
McNagny, Kelly M.
Anuria, Omphalocele, and Perinatal Lethality in Mice Lacking the Cd34-Related Protein Podocalyxin
title Anuria, Omphalocele, and Perinatal Lethality in Mice Lacking the Cd34-Related Protein Podocalyxin
title_full Anuria, Omphalocele, and Perinatal Lethality in Mice Lacking the Cd34-Related Protein Podocalyxin
title_fullStr Anuria, Omphalocele, and Perinatal Lethality in Mice Lacking the Cd34-Related Protein Podocalyxin
title_full_unstemmed Anuria, Omphalocele, and Perinatal Lethality in Mice Lacking the Cd34-Related Protein Podocalyxin
title_short Anuria, Omphalocele, and Perinatal Lethality in Mice Lacking the Cd34-Related Protein Podocalyxin
title_sort anuria, omphalocele, and perinatal lethality in mice lacking the cd34-related protein podocalyxin
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193439/
https://www.ncbi.nlm.nih.gov/pubmed/11435469
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