{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:07:46Z","timestamp":1781104066012,"version":"3.54.1"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"5","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,2,27]]},"abstract":"<jats:p>\n                    Mucopolysaccharidosis type VII (MPS VII; Sly syndrome) is an\n autosomal recessive lysosomal storage disorder due to an inherited\n deficiency of \u03b2-glucuronidase. A naturally occurring mouse model for\n this disease was discovered at The Jackson Laboratory and shown to be\n due to homozygosity for a 1-bp deletion in exon 10 of the\n                    <jats:italic>gus<\/jats:italic>\n                    gene. The murine model MPS VII\n (\n                    <jats:italic>gus<\/jats:italic>\n                    <jats:sup>mps\/mps<\/jats:sup>\n                    ) has been very well\n characterized and used extensively to evaluate experimental strategies\n for lysosomal storage diseases, including bone marrow transplantation,\n enzyme replacement therapy, and gene therapy. To enhance the value of\n this model for enzyme and gene therapy, we produced a transgenic mouse\n expressing the human \u03b2-glucuronidase cDNA with an amino acid\n substitution at the active site nucleophile (E540A) and bred it onto\n the MPS VII (\n                    <jats:italic>gus<\/jats:italic>\n                    <jats:sup>mps\/mps<\/jats:sup>\n                    ) background. We\n demonstrate here that the mutant mice bearing the active site mutant\n human transgene retain the clinical, morphological, biochemical, and\n histopathological characteristics of the original MPS VII\n (\n                    <jats:italic>gus<\/jats:italic>\n                    <jats:sup>mps\/mps<\/jats:sup>\n                    ) mouse. However, they are now\n tolerant to immune challenge with human \u03b2-glucuronidase. This\n \u201ctolerant MPS VII mouse model\u201d should be useful for preclinical\n trials evaluating the effectiveness of enzyme and\/or gene therapy\n with the human gene products likely to be administered to human\n patients with MPS VII.\n                  <\/jats:p>","DOI":"10.1073\/pnas.051623698","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:45:09Z","timestamp":1027680309000},"page":"2205-2210","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":31,"title":["Active site mutant transgene confers tolerance to human \u03b2-glucuronidase without affecting the phenotype of MPS VII mice"],"prefix":"10.1073","volume":"98","author":[{"given":"William S.","family":"Sly","sequence":"first","affiliation":[{"name":"Edward A. Doisy Department of Biochemistry and Molecular Biology\r and Department of Pathology, Saint Louis University\r School of Medicine, St. Louis, MO 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Vogler","sequence":"additional","affiliation":[{"name":"Edward A. Doisy Department of Biochemistry and Molecular Biology\r and Department of Pathology, Saint Louis University\r School of Medicine, St. Louis, MO 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey H.","family":"Grubb","sequence":"additional","affiliation":[{"name":"Edward A. Doisy Department of Biochemistry and Molecular Biology\r and Department of Pathology, Saint Louis University\r School of Medicine, St. Louis, MO 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Edward A. Doisy Department of Biochemistry and Molecular Biology\r and Department of Pathology, Saint Louis University\r School of Medicine, St. Louis, MO 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxing","family":"Jiang","sequence":"additional","affiliation":[{"name":"Edward A. Doisy Department of Biochemistry and Molecular Biology\r and Department of Pathology, Saint Louis University\r School of Medicine, St. Louis, MO 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao Yan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Edward A. Doisy Department of Biochemistry and Molecular Biology\r and Department of Pathology, Saint Louis University\r School of Medicine, St. Louis, MO 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunji","family":"Tomatsu","sequence":"additional","affiliation":[{"name":"Edward A. Doisy Department of Biochemistry and Molecular Biology\r and Department of Pathology, Saint Louis University\r School of Medicine, St. Louis, MO 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Bi","sequence":"additional","affiliation":[{"name":"Edward A. Doisy Department of Biochemistry and Molecular Biology\r and Department of Pathology, Saint Louis University\r School of Medicine, St. Louis, MO 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"Snella","sequence":"additional","affiliation":[{"name":"Edward A. Doisy Department of Biochemistry and Molecular Biology\r and Department of Pathology, Saint Louis University\r School of Medicine, St. Louis, MO 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2001,2,13]]},"reference":[{"key":"e_1_3_2_1_2","first-page":"3421","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Neufeld E F","year":"2001","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, B Childs, K W Kinzler, B Vogelstein (McGraw-Hill, 8th Ed., New York), pp. 3421\u20133452 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