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Molecular and Cellular Biology, January 2007, p. 678-688, Vol. 27, No. 2
0270-7306/07/$08.00+0     doi:10.1128/MCB.01279-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Gene Trap Disruption of the Mouse Heparan Sulfate 6-O-Endosulfatase Gene, Sulf2

Department of Anatomy, University of California, San Francisco, California 94143-0452

Received 13 July 2006/ Returned for modification 7 August 2006/ Accepted 27 October 2006

Heparan sulfate (HS) chains are found in the extracellular matrix, covalently linked to core proteins collectively termed heparan sulfate proteoglycans (HSPGs). A wealth of data has demonstrated roles for HSPGs in the regulation of many cell surface signaling pathways that are crucial during development. Variations in the sulfation pattern along the HS chains influence their ability to interact with molecules such as growth factors, chemokines, morphogens, and adhesion molecules. Sulf1 and Sulf2 are members of a class of recently identified genes that encode heparan sulfate 6-O-endosulfatases (Sulf genes). The removal of 6-O-sulfate from HS via SULF activity influences the function of many factors, including Wnt, fibroblast growth factor, hepatocyte growth factor, heparin-binding epidermal growth factor, and bone morphogenetic protein. Given their possible developmental roles, we have examined Sulf gene expression during mouse embryogenesis. The two Sulf genes are expressed in a broad range of tissues throughout development with largely nonoverlapping expression patterns. Sulf2 transcripts are expressed in the lung, heart, placenta, and ribs. We generated a mouse line possessing a gene trap disruption of the Sulf2 gene. Mice homozygous for the Sulf2 gene trap allele are viable and fertile and have no major developmental defects on several genetic backgrounds. However, we observed strain-specific, nonpenetrant defects affecting viability, lung development, and growth in Sulf2 homozygous animals. These data suggest that Sulf2 may have roles in several tissues but that there is compensation by and/or redundancy with Sulf1.

Published ahead of print on 20 November 2006.

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