{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:35:48Z","timestamp":1785803748898,"version":"3.56.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2010,12,22]],"date-time":"2010-12-22T00:00:00Z","timestamp":1292976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Hypophosphatasia (HPP) is an inherited systemic skeletal disease caused by mutations in the gene encoding the tissue-nonspecific alkaline phosphatase (TNALP) isozyme. The clinical severity of HPP varies widely, with symptoms including rickets and osteomalacia. TNALP knockout (Akp2\u2212\/\u2212) mice phenotypically mimic the severe infantile form of HPP; that is, TNALP-deficient mice are born with a normal appearance but die by 20 days of age owing to growth failure, hypomineralization, and epileptic seizures. In this study, a lentiviral vector expressing a bone-targeted form of TNALP was injected into the jugular vein of newborn Akp2\u2212\/\u2212 mice. We found that alkaline phosphatase activity in the plasma of treated Akp2\u2212\/\u2212 mice increased and remained at high levels throughout the life of the animals. The treated Akp2\u2212\/\u2212 mice survived for more than 10 months and demonstrated normal physical activity and a healthy appearance. Epileptic seizures were completely inhibited in the treated Akp2\u2212\/\u2212 mice, and X-ray examination of the skeleton showed that mineralization was significantly improved by the gene therapy. These results show that severe infantile HPP in TNALP knockout mice can be treated with a single injection of lentiviral vector during the neonatal period. \u00a9 2011 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.201","type":"journal-article","created":{"date-parts":[[2010,8,5]],"date-time":"2010-08-05T12:26:22Z","timestamp":1281011182000},"page":"135-142","source":"Crossref","is-referenced-by-count":57,"title":["Prolonged survival and phenotypic correction of <i>Akp2<\/i>\u2212<i>\/<\/i>\u2212 hypophosphatasia mice by lentiviral gene therapy"],"prefix":"10.1093","volume":"26","author":[{"given":"Seiko","family":"Yamamoto","sequence":"first","affiliation":[{"name":"Department of Pediatric Dentistry, Nihon University Graduate School of Dentistry at Matsudo, Matsudo, Japan"},{"name":"Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Orimo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Iijima","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonoko","family":"Narisawa","sequence":"additional","affiliation":[{"name":"Sanford-Burnham Medical Research Institute, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahide","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, Nihon University Graduate School of Dentistry at Matsudo, Matsudo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Luis","family":"Mill\u00e1n","sequence":"additional","affiliation":[{"name":"Sanford-Burnham Medical Research Institute, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Shimada","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,12,22]]},"reference":[{"key":"2024020318041709300_bib1","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1001\/archpedi.1948.02030020840003","article-title":"Hypophosphatasia: a new developmental anomaly","volume":"75","author":"Rathbun","year":"1948","journal-title":"Am J Dis Child."},{"key":"2024020318041709300_bib2","first-page":"439","article-title":"Hypophosphatasia and the role of alkaline phosphatase in skeletal mineralization","volume":"15","author":"Whyte","year":"1994","journal-title":"Endocr Rev."},{"key":"2024020318041709300_bib3","first-page":"5319","volume-title":"The Metabolic and Molecular Bases of Inherited Deseases","author":"Whyte","year":"2002","edition":"8th ed"},{"key":"2024020318041709300_bib4","doi-asserted-by":"crossref","first-page":"722","DOI":"10.7326\/0003-4819-65-4-722","article-title":"Hypophosphatasia: genetic and dental studies","volume":"65","author":"Pimstone","year":"1966","journal-title":"Ann Intern Med."},{"key":"2024020318041709300_bib5","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0003-9861(87)90651-5","article-title":"Hydrophobic interactions of brush border alkaline phosphatases: the role of phosphatidyl inositol","volume":"253","author":"Seetharam","year":"1987","journal-title":"Arch Biochem Biophys."},{"key":"2024020318041709300_bib6","doi-asserted-by":"crossref","DOI":"10.1002\/3527608060","volume-title":"Mammalian Alkaline Phosphatases. 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