{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:35:55Z","timestamp":1787009755870,"version":"build-2736575974"},"reference-count":52,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2018,3,19]],"date-time":"2018-03-19T00:00:00Z","timestamp":1521417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:p>\n                    A main feature of Fabry disease is nephropathy, with polyuria an early manifestation; however, the mechanism that underlies polyuria and affected tubules is unknown. To increase globotriaosylceramide (Gb3) levels, we previously crossbred asymptomatic\n                    <jats:italic>\n                      Gl\u03b1\n                      <jats:sup>tm<\/jats:sup>\n                    <\/jats:italic>\n                    mice with transgenic mice that expressed human Gb3 synthase (A4GALT) and generated the\n                    <jats:italic>\n                      Gla\n                      <jats:sup>tm<\/jats:sup>\n                      Tg(CAG\u2010A4GALT\n                    <\/jats:italic>\n                    ) symptomatic Fabry model mice. Additional analyses revealed that these mice exhibit polyuria and renal dysfunction without remarkable glomerular damage. In the present study, we investigated the mechanism of polyuria and renal dysfunction in these mice. Gb3 accumulation was mostly detected in the medulla; medullary thick ascending limbs (mTALs) were the most vacuolated tubules. mTAL cells contained lamellar bodies and had lost their characteristic structure\n                    <jats:italic>(i.e<\/jats:italic>\n                    ., extensive infolding and numerous elongated mitochondria). Decreased expression of the major molecules\u2014Na\n                    <jats:sup>+<\/jats:sup>\n                    \u2010K\n                    <jats:sup>+<\/jats:sup>\n                    \u2010ATPase, uromodulin, and Na\n                    <jats:sup>+<\/jats:sup>\n                    \u2010K\n                    <jats:sup>+<\/jats:sup>\n                    \u20102Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    cotransporter\u2014that are involved in Na+ reabsorption in mTALs and the associated loss of urine\u2010concentrating ability resulted in progressive water\u2010 and salt\u2010loss phenotypes.\n                    <jats:italic>\n                      Gla\n                      <jats:sup>tm<\/jats:sup>\n                      Tg(CAG\u2010A4GALT\n                    <\/jats:italic>\n                    ) mice exhibited fibrosis around mTALs and renal dysfunction. These and other features were consistent with pathologic findings in patients with Fabry disease. Results demonstrate that mTAL dysfunction causes polyuria and renal impairment and contributes to the pathophysiology of Fabry nephropathy.\u2014Maruyama, H., Taguchi, A., Nishikawa, Y., Guili, C., Mikame, M., Nameta, M., Yamaguchi, Y., Ueno, M., Imai, N., Ito, Y., Nakagawa, T., Narita, I., Ishii, S. Medullary thick ascending limb impairment in the\n                    <jats:italic>GlatmTg(CAG\u2010A4GALT<\/jats:italic>\n                    ) Fabry model mice.\n                    <jats:italic>FASEB J<\/jats:italic>\n                    . 32, 4544\u20134559 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201701374r","type":"journal-article","created":{"date-parts":[[2018,3,19]],"date-time":"2018-03-19T13:50:34Z","timestamp":1521467434000},"page":"4544-4559","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Medullary thick ascending limb impairment in the\n                    <i>\n                      Gla\n                      <sup>tm<\/sup>\n                      Tg(CAG\u2010A4GALT\n                    <\/i>\n                    ) Fabry model mice"],"prefix":"10.1096","volume":"32","author":[{"given":"Hiroki","family":"Maruyama","sequence":"first","affiliation":[{"name":"Department of Clinical Nephroscience Electron Microscope Core Facility Niigata University Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsumi","family":"Taguchi","sequence":"additional","affiliation":[{"name":"Department of Clinical Nephroscience Electron Microscope Core Facility Niigata University Niigata Japan"},{"name":"Department of Matrix Medicine Faculty of Medicine Oita University Yufu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Nishikawa","sequence":"additional","affiliation":[{"name":"Division of Tumor Pathology Department of Pathology Asahikawa Medical University Asahikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chu","family":"Guili","sequence":"additional","affiliation":[{"name":"Department of Clinical Nephroscience Electron Microscope Core Facility Niigata University Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Mikame","sequence":"additional","affiliation":[{"name":"Department of Clinical Nephroscience Electron Microscope Core Facility Niigata University Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Nameta","sequence":"additional","affiliation":[{"name":"Electron Microscope Core Facility Niigata University Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Yamaguchi's Pathology Laboratory Matsudo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuhiro","family":"Ueno","sequence":"additional","affiliation":[{"name":"University Health Center Joetsu University of Education Joetsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naofumi","family":"Imai","sequence":"additional","affiliation":[{"name":"Division of Clinical Nephrology and Rheumatology Electron Microscope Core Facility Niigata University Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Health Promotion Medicine Niigata University Graduate School of Medical and Dental Sciences Electron Microscope Core Facility Niigata University Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiko","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Future Basic Medicine Nara Medical University Kashihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiei","family":"Narita","sequence":"additional","affiliation":[{"name":"Division of Clinical Nephrology and Rheumatology Electron Microscope Core Facility Niigata University Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Matrix Medicine Faculty of Medicine Oita University Yufu Japan"},{"name":"GlycoPharma Corporation Oita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM196705252762101"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00008196"},{"key":"e_1_2_8_4_1","unstructured":"The Human Gene Mutation Database.GLA.Available at:http:\/\/www.hgmd.cf.ac.uk\/ac\/gene.php?gene=GLA. 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