{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T02:00:41Z","timestamp":1791165641517,"version":"4.1.0"},"reference-count":41,"publisher":"National Academy of Sciences","issue":"25","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,12,7]]},"abstract":"<jats:p>\n                    The Sanfilippo syndrome type B is an autosomal recessive disorder caused by mutation in the gene (\n                    <jats:italic>NAGLU<\/jats:italic>\n                    ) encoding \u03b1-\n                    <jats:italic>N<\/jats:italic>\n                    -acetylglucosaminidase, a lysosomal enzyme required for the stepwise degradation of heparan sulfate. The most serious manifestations are profound mental retardation, intractable behavior problems, and death in the second decade. To generate a model for studies of pathophysiology and of potential therapy, we disrupted exon 6 of\n                    <jats:italic>Naglu<\/jats:italic>\n                    , the homologous mouse gene.\n                    <jats:italic>Naglu\u2212\/\u2212<\/jats:italic>\n                    mice were healthy and fertile while young and could survive for 8\u201312 mo. They were totally deficient in \u03b1-\n                    <jats:italic>N<\/jats:italic>\n                    -acetylglucosaminidase and had massive accumulation of heparan sulfate in liver and kidney as well as secondary changes in activity of several other lysosomal enzymes in liver and brain and elevation of gangliosides G\n                    <jats:sub>M2<\/jats:sub>\n                    and G\n                    <jats:sub>M3<\/jats:sub>\n                    in brain. Vacuolation was seen in many cells, including macrophages, epithelial cells, and neurons, and became more prominent with age. Although most vacuoles contained finely granular material characteristic of glycosaminoglycan accumulation, large pleiomorphic inclusions were seen in some neurons and pericytes in the brain. Abnormal hypoactive behavior was manifested by 4.5-mo-old\n                    <jats:italic>Naglu\u2212\/\u2212<\/jats:italic>\n                    mice in an open field test; the hyperactivity that is characteristic of affected children was not observed even in younger mice. In a Pavlovian fear conditioning test, the 4.5-mo-old mutant mice showed normal response to context, indicating intact hippocampal-dependent learning, but reduced response to a conditioning tone, perhaps attributable to hearing impairment. The phenotype of the \u03b1-\n                    <jats:italic>N<\/jats:italic>\n                    -acetylglucosaminidase-deficient mice is sufficiently similar to that of patients with the Sanfilippo syndrome type B to make these mice a good model for study of pathophysiology and for development of therapy.\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.25.14505","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:39:15Z","timestamp":1027679955000},"page":"14505-14510","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":187,"title":["Mouse model of Sanfilippo syndrome type B produced by targeted disruption of the gene encoding \u03b1-\n                    <i>N<\/i>\n                    -acetylglucosaminidase"],"prefix":"10.1073","volume":"96","author":[{"given":"Hong Hua","family":"Li","sequence":"first","affiliation":[{"name":"Departments of Biological Chemistry, Pathology and Laboratory Medicine, Orthopaedic Surgery, Psychology, Brain Research Institute, and Molecular Biology Institute, University of California, Los Angeles, CA 90095; Neuroscience Center and Departments of Neurology and Psychiatry, University of North Carolina, Chapel Hill, NC 27599; and Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U189, Lyon-Sud School of Medicine, Oullins, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Hong","family":"Yu","sequence":"additional","affiliation":[{"name":"Departments of Biological Chemistry, Pathology and Laboratory Medicine, Orthopaedic Surgery, Psychology, Brain Research Institute, and Molecular Biology Institute, University of California, Los Angeles, CA 90095; Neuroscience Center and Departments of Neurology and Psychiatry, University of North Carolina, Chapel Hill, NC 27599; and Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U189, Lyon-Sud School of Medicine, Oullins, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Rozengurt","sequence":"additional","affiliation":[{"name":"Departments of Biological Chemistry, Pathology and Laboratory Medicine, Orthopaedic Surgery, Psychology, Brain Research Institute, and Molecular Biology Institute, University of California, Los Angeles, CA 90095; Neuroscience Center and Departments of Neurology and Psychiatry, University of North Carolina, Chapel Hill, NC 27599; and Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U189, Lyon-Sud School of Medicine, Oullins, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Zhi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Departments of Biological Chemistry, Pathology and Laboratory Medicine, Orthopaedic Surgery, Psychology, Brain Research Institute, and Molecular Biology Institute, University of California, Los Angeles, CA 90095; Neuroscience Center and Departments of Neurology and Psychiatry, University of North Carolina, Chapel Hill, NC 27599; and Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U189, Lyon-Sud School of Medicine, Oullins, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen M.","family":"Lyons","sequence":"additional","affiliation":[{"name":"Departments of Biological Chemistry, Pathology and Laboratory Medicine, Orthopaedic Surgery, Psychology, Brain Research Institute, and Molecular Biology Institute, University of California, Los Angeles, CA 90095; Neuroscience Center and Departments of Neurology and Psychiatry, University of North Carolina, Chapel Hill, NC 27599; and Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U189, Lyon-Sud School of Medicine, Oullins, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Anagnostaras","sequence":"additional","affiliation":[{"name":"Departments of Biological Chemistry, Pathology and Laboratory Medicine, Orthopaedic Surgery, Psychology, Brain Research Institute, and Molecular Biology Institute, University of California, Los Angeles, CA 90095; Neuroscience Center and Departments of Neurology and Psychiatry, University of North Carolina, Chapel Hill, NC 27599; and Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U189, Lyon-Sud School of Medicine, Oullins, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Fanselow","sequence":"additional","affiliation":[{"name":"Departments of Biological Chemistry, Pathology and Laboratory Medicine, Orthopaedic Surgery, Psychology, Brain Research Institute, and Molecular Biology Institute, University of California, Los Angeles, CA 90095; Neuroscience Center and Departments of Neurology and Psychiatry, University of North Carolina, Chapel Hill, NC 27599; and Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U189, Lyon-Sud School of Medicine, Oullins, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunihiko","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Departments of Biological Chemistry, Pathology and Laboratory Medicine, Orthopaedic Surgery, Psychology, Brain Research Institute, and Molecular Biology Institute, University of California, Los Angeles, CA 90095; Neuroscience Center and Departments of Neurology and Psychiatry, University of North Carolina, Chapel Hill, NC 27599; and Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U189, Lyon-Sud School of Medicine, Oullins, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie T.","family":"Vanier","sequence":"additional","affiliation":[{"name":"Departments of Biological Chemistry, Pathology and Laboratory Medicine, Orthopaedic Surgery, Psychology, Brain Research Institute, and Molecular Biology Institute, University of California, Los Angeles, CA 90095; 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