{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:36:23Z","timestamp":1791272183192,"version":"4.1.0"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"52","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,12,26]]},"abstract":"<jats:p>\n                    Discs-large homolog 1 (DLGH1) is a mouse ortholog of the\n                    <jats:italic>Drosophila<\/jats:italic>\n                    discs-large (DLG) tumor suppressor protein, a founding member of the PDZ and MAGUK protein families. DLG proteins play important roles in regulating cell proliferation, epithelial cell polarity, and synapse formation and function. Here, we generated a null allele of\n                    <jats:italic>Dlgh1<\/jats:italic>\n                    and studied its role in urogenital development.\n                    <jats:italic>Dlgh1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice developed severe urinary tract abnormalities, including congenital hydronephrosis, which is the leading cause of renal failure in infants and children. DLGH1 is expressed in the developing ureter; in its absence, the stromal cells that normally lie between the urothelial and smooth muscle layers were missing. Moreover, in ureteric smooth muscle, the circular smooth muscle cells were misaligned in a longitudinal orientation. These abnormalities in the ureter led to severely impaired ureteric peristalsis. Similar smooth muscle defects are observed frequently in patients with ureteropelvic junction obstruction, a common form of hydronephrosis. Our results suggest that (\n                    <jats:italic>i<\/jats:italic>\n                    ) besides its well documented role in regulating epithelial polarity,\n                    <jats:italic>Dlgh1<\/jats:italic>\n                    also regulates smooth muscle orientation, and (\n                    <jats:italic>ii<\/jats:italic>\n                    ) human\n                    <jats:italic>DLG1<\/jats:italic>\n                    mutations may contribute to hereditary forms of hydronephrosis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0609326103","type":"journal-article","created":{"date-parts":[[2006,12,15]],"date-time":"2006-12-15T20:58:28Z","timestamp":1166216308000},"page":"19872-19877","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":100,"title":["Discs-large homolog 1 regulates smooth muscle orientation in the mouse ureter"],"prefix":"10.1073","volume":"103","author":[{"given":"Zhen X.","family":"Mahoney","sequence":"first","affiliation":[{"name":"*Department of Internal Medicine, Renal Division, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9n\u00e9dicte","family":"Sammut","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramnik J.","family":"Xavier","sequence":"additional","affiliation":[{"name":"Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanette","family":"Cunningham","sequence":"additional","affiliation":[{"name":"*Department of Internal Medicine, Renal Division, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloriosa","family":"Go","sequence":"additional","affiliation":[{"name":"*Department of Internal Medicine, Renal Division, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karry L.","family":"Brim","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thaddeus S.","family":"Stappenbeck","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey H.","family":"Miner","sequence":"additional","affiliation":[{"name":"*Department of Internal Medicine, Renal Division, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Swat","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110; 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