{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:13:07Z","timestamp":1781107987614,"version":"3.54.1"},"reference-count":47,"publisher":"National Academy of Sciences","issue":"4","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1997,2,18]]},"abstract":"<jats:p>Mucopolysaccharidosis type VII (Sly syndrome) is a lysosomal storage disease caused by inherited deficiency of the lysosomal enzyme \u03b2-glucuronidase. A murine model of this disorder has been well characterized and used to study a number of forms of experimental therapies, including gene therapy. We produced recombinant adenovirus that expresses human \u03b2-glucuronidase and administered this recombinant adenovirus to \u03b2-glucuronidase-deficient mice intravenously. The \u03b2-glucuronidase activities in liver and spleen were elevated to 40% and 20%, respectively, of the heterozygote enzymatic level at day 16. Expression persisted for at least 35 days. Pathological abnormalities of these tissues were also improved, and the elevated levels of urinary glycosaminoglycans were reduced in treated mice. However, the \u03b2-glucuronidase activity in kidney and brain was not significantly increased. After administration of the recombinant adenovirus directly into the lateral ventricles of mutant mice, the \u03b2-glucuronidase activity in crude brain homogenates increased to 30% of heterozygote activity. Histochemical demonstration of \u03b2-glucuronidase activity in brain revealed that the enzymatic activity was mainly in ependymal cells and choroid. However, in some regions, the adenovirus-mediated gene expression was also evident in brain parenchyma associated with vessels and in the meninges. These results suggest that adenovirus-mediated gene delivery might improve the central nervous system pathology of mucopolysaccharidosis in addition to correcting visceral pathology.<\/jats:p>","DOI":"10.1073\/pnas.94.4.1287","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:35:50Z","timestamp":1027679750000},"page":"1287-1292","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":94,"title":["Adenovirus-mediated gene transfer and expression of human \u03b2-glucuronidase gene in the liver, spleen, and central nervous system in mucopolysaccharidosis type\u2009VII\u2009mice"],"prefix":"10.1073","volume":"94","author":[{"given":"Toya","family":"Ohashi","sequence":"first","affiliation":[{"name":"Departments of Pediatrics and Gene Therapy, Institute of DNA Medicine, and Division of Neuropathology, Institutes of Neuroscience, The Jikei University School of Medicine, 3-25-8 Nishishinbashi, Minatoku, Tokyo 105, Japan; and The Edward A. Doisy Department of Biochemistry and Molecular Biology, and Department of Pathology, St. Louis University School of Medicine, 1402 South Grand Boulevard, St. Louis, MO 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Watabe","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Gene Therapy, Institute of DNA Medicine, and Division of Neuropathology, Institutes of Neuroscience, The Jikei University School of Medicine, 3-25-8 Nishishinbashi, Minatoku, Tokyo 105, Japan; and The Edward A. Doisy Department of Biochemistry and Molecular Biology, and Department of Pathology, St. Louis University School of Medicine, 1402 South Grand Boulevard, St. Louis, MO 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Uehara","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Gene Therapy, Institute of DNA Medicine, and Division of Neuropathology, Institutes of Neuroscience, The Jikei University School of Medicine, 3-25-8 Nishishinbashi, Minatoku, Tokyo 105, Japan; and The Edward A. Doisy Department of Biochemistry and Molecular Biology, and Department of Pathology, St. Louis University School of Medicine, 1402 South Grand Boulevard, St. Louis, MO 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William\u2009S.","family":"Sly","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Gene Therapy, Institute of DNA Medicine, and Division of Neuropathology, Institutes of Neuroscience, The Jikei University School of Medicine, 3-25-8 Nishishinbashi, Minatoku, Tokyo 105, Japan; and The Edward A. Doisy Department of Biochemistry and Molecular Biology, and Department of Pathology, St. Louis University School of Medicine, 1402 South Grand Boulevard, St. Louis, MO 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Vogler","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Gene Therapy, Institute of DNA Medicine, and Division of Neuropathology, Institutes of Neuroscience, The Jikei University School of Medicine, 3-25-8 Nishishinbashi, Minatoku, Tokyo 105, Japan; and The Edward A. Doisy Department of Biochemistry and Molecular Biology, and Department of Pathology, St. Louis University School of Medicine, 1402 South Grand Boulevard, St. Louis, MO 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshikatsu","family":"Eto","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Gene Therapy, Institute of DNA Medicine, and Division of Neuropathology, Institutes of Neuroscience, The Jikei University School of Medicine, 3-25-8 Nishishinbashi, Minatoku, Tokyo 105, Japan; and The Edward A. Doisy Department of Biochemistry and Molecular Biology, and Department of Pathology, St. Louis University School of Medicine, 1402 South Grand Boulevard, St. Louis, MO 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1997,2,18]]},"reference":[{"key":"e_1_3_2_1_2","first-page":"2465","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Neufeld E F","year":"1995","unstructured":"E F Neufeld, J Muenzer The Metabolic and Molecular Bases of Inherited Disease, eds C R Scriver, A L Beaudet, W S Sly, D Valle (McGraw\u2013Hill, 7th Ed., New York), pp. 2465\u20132494 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