{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:26:25Z","timestamp":1781105185343,"version":"3.54.1"},"reference-count":54,"publisher":"National Academy of Sciences","issue":"2","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,1,13]]},"abstract":"<jats:p>\n                    Cardiovascular manifestations of lysosomal storage disease (LSD) are a significant health problem for affected patients. Infantileonset cardiac disease, because of its rapid progression, is usually treated symptomatically. Therapy in older patients includes valve replacement and bone marrow (BM) transplantation, both of which are life threatening in the already debilitated patients. Enzyme replacement therapy has potential benefit but has not yet been demonstrated to provide long-term relief for cardiac disease. Here, we demonstrate prevention of severe cardiac manifestations in \u03b2-glucuronidase (GUSB) null mice BM-transplanted i.v. as neonates without myeloablative pretreatment. The mice, a model of mucopolysaccharidosis type VII (MPSVII, Sly syndrome), develop progressive LSD unless provided with GUSB early in life. The BM recipients retained GUSB+ donor cells in the peripheral blood and heart until necropsy at &gt;11 months of age. The enzyme \u03b2-hexosamindase increased in tissues of GUSB null MPSVII mice was reduced significantly (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.001) in treated MPSVII hearts. Electrocardiography demonstrated normalization of heart rate, PR, PQ, and QRS intervals in BM recipients. Storage was markedly reduced in the stroma of heart valves, adventitial cells of the aortic root, perivascular and interstitial cells of the myocardium, and interstitial cells of the conduction tissue. Heart\/body weight ratio normalized. The aortic root was still grossly distended, and the conductive myocytes retained storage, suggesting neither plays a major role in ECG normalization. We conclude that transplantation of MPSVII neonates without toxic intervention can prevent many of the cardiovascular manifestations of LSD.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0305284101","type":"journal-article","created":{"date-parts":[[2004,1,13]],"date-time":"2004-01-13T13:28:06Z","timestamp":1074000486000},"page":"603-608","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":12,"title":["Electrocardiographic and other cardiac anomalies in \u03b2-glucuronidase-null mice corrected by nonablative neonatal marrow transplantation"],"prefix":"10.1073","volume":"101","author":[{"given":"A. J. T.","family":"Schuldt","sequence":"first","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609; Mouse Specifics, P.O. Box 200821, Boston, MA 02109; and Department of Pathology, Saint Louis University Medical School, St. Louis, MO 63101"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. J.","family":"Hampton","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609; Mouse Specifics, P.O. Box 200821, Boston, MA 02109; and Department of Pathology, Saint Louis University Medical School, St. Louis, MO 63101"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Chu","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609; Mouse Specifics, P.O. Box 200821, Boston, MA 02109; and Department of Pathology, Saint Louis University Medical School, St. Louis, MO 63101"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. A.","family":"Vogler","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609; Mouse Specifics, P.O. Box 200821, Boston, MA 02109; and Department of Pathology, Saint Louis University Medical School, St. Louis, MO 63101"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Galvin","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609; Mouse Specifics, P.O. Box 200821, Boston, MA 02109; and Department of Pathology, Saint Louis University Medical School, St. Louis, MO 63101"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. D.","family":"Lessard","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609; Mouse Specifics, P.O. Box 200821, Boston, MA 02109; and Department of Pathology, Saint Louis University Medical School, St. Louis, MO 63101"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. E.","family":"Barker","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609; Mouse Specifics, P.O. 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