{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:18:39Z","timestamp":1791278319010,"version":"4.1.0"},"reference-count":76,"publisher":"Cold Spring Harbor Laboratory","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Dev."],"published-print":{"date-parts":[[1998,6,15]]},"abstract":"<jats:p>Heparan sulfate proteoglycans have been implicated in the presentation of a number of secreted signaling molecules to their signal-transducing receptors. We have characterized a gene trap mutation in the gene encoding a heparan sulfate biosynthetic enzyme, heparan sulfate 2-sulfotransferase (HS2ST). Transgenic mice were generated from embryonic stem cells harboring this insertion.<jats:italic>lacZ<\/jats:italic> reporter gene activity in heterozygous embryos demonstrates that the gene is expressed differentially during embryogenesis, presumably directing dynamic changes in heparan sulfate structure. Moreover, mice homozygous for the <jats:italic>Hs2st<\/jats:italic> gene trap allele die in the neonatal period, exhibiting bilateral renal agenesis and defects of the eye and the skeleton. Analysis of kidney development in <jats:italic>Hs2st<\/jats:italic> mutants reveals that the gene is not required for two early events\u2014ureteric bud outgrowth from the Wolffian duct and initial induction of Pax-2 expression in the metanephric mesenchyme. It is required, however, for mesenchymal condensation around the ureteric bud and initiation of branching morphogenesis. Because 2-<jats:italic>O<\/jats:italic>-sulfation has been shown to influence the functional interactions of ligands with heparan sulfate in vitro, we discuss the possibility that the <jats:italic>Hs2st<\/jats:italic> mutant phenotype is a consequence of compromised interactions between growth factors and their signal-transducing receptors. These data provide the first genetic evidence that the regulated synthesis of differentially glycosylated proteoglycans can affect morphogenesis during vertebrate development.<\/jats:p>","DOI":"10.1101\/gad.12.12.1894","type":"journal-article","created":{"date-parts":[[2008,2,20]],"date-time":"2008-02-20T22:52:17Z","timestamp":1203547937000},"page":"1894-1906","source":"Crossref","is-referenced-by-count":391,"title":["Renal agenesis in mice homozygous for a gene trap mutation in the gene encoding heparan sulfate\u20092-sulfotransferase"],"prefix":"10.1101","volume":"12","author":[{"given":"Simon L.","family":"Bullock","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy M.","family":"Fletcher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa S.P.","family":"Beddington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie A.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[1998,6,15]]},"reference":[{"key":"2021111418543472000_12.12.1894.1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1990.9999"},{"key":"2021111418543472000_12.12.1894.2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.30.17711"},{"key":"2021111418543472000_12.12.1894.3","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.37.23172"},{"key":"2021111418543472000_12.12.1894.4","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1006\/scdb.1996.0026","article-title":"Kidney development: The inductive interactions.","volume":"7","author":"Bard","year":"1996","journal-title":"Sem. 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