{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:39:24Z","timestamp":1791898764409,"version":"4.3.4"},"reference-count":51,"publisher":"National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,4,28]]},"abstract":"<jats:p>\n                    <jats:italic>Npt2<\/jats:italic>\n                    encodes a renal-specific, brush-border membrane\n Na\n                    <jats:sup>+<\/jats:sup>\n                    -phosphate (P\n                    <jats:sub>i<\/jats:sub>\n                    ) cotransporter that is\n expressed in the proximal tubule where the bulk of filtered\n P\n                    <jats:sub>i<\/jats:sub>\n                    is reabsorbed. Mice deficient in the\n                    <jats:italic>Npt2<\/jats:italic>\n                    gene were generated by targeted mutagenesis to define the role of\n                    <jats:italic>Npt2<\/jats:italic>\n                    in the overall maintenance of P\n                    <jats:sub>i<\/jats:sub>\n                    homeostasis, determine its impact on skeletal development, and clarify\n its relationship to autosomal disorders of renal P\n                    <jats:sub>i<\/jats:sub>\n                    reabsorption in humans. Homozygous mutants\n (\n                    <jats:italic>Npt2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) exhibit increased urinary\n P\n                    <jats:sub>i<\/jats:sub>\n                    excretion, hypophosphatemia, an appropriate elevation in\n the serum concentration of 1,25-dihydroxyvitamin D with attendant\n hypercalcemia, hypercalciuria and decreased serum parathyroid hormone\n levels, and increased serum alkaline phosphatase activity. These\n biochemical features are typical of patients with hereditary\n hypophosphatemic rickets with hypercalciuria (HHRH), a Mendelian\n disorder of renal P\n                    <jats:sub>i<\/jats:sub>\n                    reabsorption. However, unlike HHRH\n patients,\n                    <jats:italic>Npt2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice do not have rickets\n or osteomalacia. At weaning,\n                    <jats:italic>Npt2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice\n have poorly developed trabecular bone and retarded secondary\n ossification, but, with increasing age, there is a dramatic reversal\n and eventual overcompensation of the skeletal phenotype. Our findings\n demonstrate that\n                    <jats:italic>Npt2<\/jats:italic>\n                    is a major regulator of\n P\n                    <jats:sub>i<\/jats:sub>\n                    homeostasis and necessary for normal skeletal\n development.\n                  <\/jats:p>","DOI":"10.1073\/pnas.95.9.5372","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:31:44Z","timestamp":1027679504000},"page":"5372-5377","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":533,"title":["Targeted inactivation of\n                    <i>Npt2<\/i>\n                    in mice leads to severe renal phosphate wasting, hypercalciuria, and skeletal abnormalities"],"prefix":"10.1073","volume":"95","author":[{"given":"Laurent","family":"Beck","sequence":"first","affiliation":[{"name":"Departments of Pediatrics and Human Genetics, McGill University,\r Montreal Children\u2019s Hospital Research Institute, Montreal, PQ, Canada\r H3H 1P3; Division of Endocrinology, Sir Mortimer B.\r Davis-Jewish General Hospital, Lady Davis Institute for Medical\r Research, Department of Medicine, McGill University, Montreal, PQ\r Canada H3T 1E2; and First Department of Oral Anatomy, Niigata\r University School of Dentistry, Niigata 951-8514, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C.","family":"Karaplis","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Human Genetics, McGill University,\r Montreal Children\u2019s Hospital Research Institute, Montreal, PQ, Canada\r H3H 1P3; Division of Endocrinology, Sir Mortimer B.\r Davis-Jewish General Hospital, Lady Davis Institute for Medical\r Research, Department of Medicine, McGill University, Montreal, PQ\r Canada H3T 1E2; and First Department of Oral Anatomy, Niigata\r University School of Dentistry, Niigata 951-8514, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norio","family":"Amizuka","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Human Genetics, McGill University,\r Montreal Children\u2019s Hospital Research Institute, Montreal, PQ, Canada\r H3H 1P3; Division of Endocrinology, Sir Mortimer B.\r Davis-Jewish General Hospital, Lady Davis Institute for Medical\r Research, Department of Medicine, McGill University, Montreal, PQ\r Canada H3T 1E2; and First Department of Oral Anatomy, Niigata\r University School of Dentistry, Niigata 951-8514, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Stacy","family":"Hewson","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Human Genetics, McGill University,\r Montreal Children\u2019s Hospital Research Institute, Montreal, PQ, Canada\r H3H 1P3; Division of Endocrinology, Sir Mortimer B.\r Davis-Jewish General Hospital, Lady Davis Institute for Medical\r Research, Department of Medicine, McGill University, Montreal, PQ\r Canada H3T 1E2; and First Department of Oral Anatomy, Niigata\r University School of Dentistry, Niigata 951-8514, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidehiro","family":"Ozawa","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Human Genetics, McGill University,\r Montreal Children\u2019s Hospital Research Institute, Montreal, PQ, Canada\r H3H 1P3; Division of Endocrinology, Sir Mortimer B.\r Davis-Jewish General Hospital, Lady Davis Institute for Medical\r Research, Department of Medicine, McGill University, Montreal, PQ\r Canada H3T 1E2; and First Department of Oral Anatomy, Niigata\r University School of Dentistry, Niigata 951-8514, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harriet S.","family":"Tenenhouse","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Human Genetics, McGill University,\r Montreal Children\u2019s Hospital Research Institute, Montreal, PQ, Canada\r H3H 1P3; Division of Endocrinology, Sir Mortimer B.\r Davis-Jewish General Hospital, Lady Davis Institute for Medical\r Research, Department of Medicine, McGill University, Montreal, PQ\r Canada H3T 1E2; and First Department of Oral Anatomy, Niigata\r University School of Dentistry, Niigata 951-8514, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1998,4,28]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1985.65.2.431"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1991.260.5.C885"},{"key":"e_1_3_2_3_2","first-page":"2511","volume-title":"The Kidney: Physiology and Pathophysiology","author":"Berndt T J","year":"1992","unstructured":"T J Berndt, F G Knox The Kidney: Physiology and Pathophysiology, eds D W Seldin, G Giebisch (Raven, New York), pp. 2511\u20132532 (1992)."},{"key":"e_1_3_2_4_2","first-page":"F226","volume":"252","author":"Walker J J","year":"1987","unstructured":"J J Walker, T S Yan, G A Quamme Am J Physiol 252, F226\u2013F231 (1987).","journal-title":"Am J Physiol"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.21.9608"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1993.1476"},{"key":"e_1_3_2_7_2","first-page":"F1038","volume":"268","author":"Chong S S","year":"1995","unstructured":"S S Chong, C A Kozak, L Liu, K Kristjansson, S T Dunn, J E Bourdeau, M R Hughes Am J Physiol 268, F1038\u2013F1045 (1995).","journal-title":"Am J Physiol"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.13.5979"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)37417-3"},{"key":"e_1_3_2_10_2","first-page":"F626","volume":"268","author":"Verri T","year":"1995","unstructured":"T Verri, D Markovich, C Perego, F Norbis, G Stange, V Sorribas, J Biber, H Murer Am J Physiol 268, F626\u2013F633 (1995).","journal-title":"Am J Physiol"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.8.11.8070635"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00386183"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1995.tb20341.x"},{"key":"e_1_3_2_14_2","first-page":"F900","volume":"267","author":"Levi M","year":"1994","unstructured":"M Levi, M Lotscher, V Sorribas, M Custer, M Arar, B Kaissling, H Murer, J Biber Am J Physiol 267, F900\u2013F908 (1994).","journal-title":"Am J Physiol"},{"key":"e_1_3_2_15_2","first-page":"F784","volume":"268","author":"Kempson S A","year":"1995","unstructured":"S A Kempson, M Lotscher, B Kaissling, J Biber, H Murer, M Levi Am J Physiol 268, F784\u2013F791 (1995).","journal-title":"Am J Physiol"},{"key":"e_1_3_2_16_2","volume-title":"Mendelian Inheritance in Man","author":"McKusick V A","year":"1992","unstructured":"V A McKusick Mendelian Inheritance in Man (Johns Hopkins Univ. 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