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PMID: 11435469 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of experimental medicine ·Vol. 194 ·No. 1 ·2001-07-02 ·Pages 13-27

Doyonnas R, Kershaw DB, Duhme C, Merkens H, Chelliah S, Graf T, McNagny KM

Abstract

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.

MeSH Terms
Animals Antigens, CD34/metabolism Anuria/genetics Blood Vessels/embryology,metabolism Diaphragm/abnormalities Edema/genetics Female Fetal Death/genetics Gene Expression Regulation, Developmental Hematopoietic System/embryology,metabolism Hernia, Umbilical/genetics Kidney/abnormalities,pathology Male Mice Mice, Mutant Strains Renal Insufficiency/genetics Sialoglycoproteins/genetics,metabolism
Chemicals
Antigens, CD34 Sialoglycoproteins podocalyxin
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Doyonnas R
The Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada.
Kershaw D B
Duhme C
Merkens H
Chelliah S
Graf T
McNagny K M
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.194.1.13
Published
2001-07-02
Pages
13-27
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2193439
Subset
IM
Grants
NIDDK NIH HHS · DK02264-01A1 · United States
External Links
PubMed source DOI: 10.1084/jem.194.1.13 PMC Full Text View journal details
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