Role of sodium-dependent Pi transporter/Npt2c on Pi homeostasis in klotho knockout mice different properties between juvenile and adult stages

• Material Type: 博士論文
• Title: Role of sodium-dependent Pi transporter/Npt2c on Pi homeostasis in klotho knockout mice different properties between juvenile and adult stages
• Author/Editor: Hanazaki, Ai; Ikuta, Kayo; Sasaki, Shohei; Sasaki, Sumire; Koike, Megumi; Tanifuji, Kazuya; Arima, Yuki; Kaneko, Ichiro; Shiozaki, Yuji; Tatsumi, Sawako; Hasegawa, Tomoka; Amizuka, Norio; Miyamoto, Ken-ichi; Segawa, Hiroko
• Author Heading: Hanazaki, Ai; Ikuta, Kayo; Sasaki, Shohei; Sasaki, Sumire; Koike, Megumi; Tanifuji, Kazuya; Arima, Yuki; Kaneko, Ichiro; Shiozaki, Yuji; Tatsumi, Sawako; Hasegawa, Tomoka; Amizuka, Norio; Miyamoto, Ken-ichi; Segawa, Hiroko
• Publication, Distribution, etc.: Wiley|The Physiological Society|The American Physiological Society
• Publication Date: 2020-02-05
• Publication Date (W3CDTF): 2020-02-05
• Alternative Title: Na依存性PiトランスポーターNpt2cは、KlothoノックアウトマウスPi恒常性において成長期と成熟期では異なる作用を有する
• Periodical title: Physiological Reports
• No. or year of volume/issue: 8 3
• Volume: 8
• Issue: 3
• Pages: e14324-
• ISSN (Periodical Title): ISSN : 2051-817X
• Degree grantor/type: 徳島大学
• Date Granted: 2020-01-23
• Dissertation Number: 甲第3346号
• Degree Type: 博士（栄養学）
• Text Language Code: eng
• Subject Heading: Phosphate; klotho; Npt2c; HHRH; juvenile; FGF23/klotho; growth; intestine; kidney; phosphate transporter
• Target Audience: 一般
• Note (General): SLC34A3/NPT2c/NaPi-2c/Npt2c is a growth-related NaPi cotransporter that mediates the uptake of renal sodium-dependent phosphate (Pi). Mutation of human NPT2c causes hereditary hypophosphatemic rickets with hypercalciuria. Mice with Npt2c knockout, however, exhibit normal Pi metabolism. To investigate the role of Npt2c in Pi homeostasis, we generated α-klotho−/−/Npt2c−/− (KL2cDKO) mice and analyzed Pi homeostasis. α-Klotho−/− (KLKO) mice exhibit hyperphosphatemia and markedly increased kidney Npt2c protein levels. Genetic disruption of Npt2c extended the lifespan of KLKO mice similar to that of α-Klotho−/−/Npt2a−/− mice. Adult KL2cDKO mice had hyperphosphatemia, but analysis of Pi metabolism revealed significantly decreased intestinal and renal Pi (re)absorption compared with KLKO mice. The 1,25-dihydroxy vitamin D3 concentration was not reduced in KL2cDKO mice compared with that in KLKO mice. The KL2cDKO mice had less severe soft tissue and vascular calcification compared with KLKO mice. Juvenile KL2cDKO mice had significantly reduced plasma Pi levels, but Pi metabolism was not changed. In Npt2cKO mice, plasma Pi levels began to decrease around the age of 15 days and significant hypophosphatemia developed within 21 days. The findings of the present study suggest that Npt2c contributes to regulating plasma Pi levels in the juvenile stage and affects Pi retention in the soft and vascular tissues in KLKO mice.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): This is an open access article under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/ ), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
• Related Material (DOI): 10.14814/phy2.14324
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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