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ID 114243
Title Alternative
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
Author
Hanazaki, Ai Tokushima University
Ikuta, Kayo Tokushima University
Sasaki, Shohei Tokushima University
Sasaki, Sumire Tokushima University
Koike, Megumi Tokushima University
Tanifuji, Kazuya Tokushima University
Arima, Yuki Tokushima University
Hasegawa, Tomoka Hokkaido University
Amizuka, Norio Hokkaido University
Keywords
Phosphate
klotho
Npt2c
HHRH
juvenile
FGF23/klotho
growth
intestine
kidney
phosphate transporter
Content Type
Thesis or Dissertation
Description
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.
Journal Title
Physiological Reports
ISSN
2051817X
Publisher
Wiley|The Physiological Society|The American Physiological Society
Volume
8
Issue
3
Start Page
e14324
Published Date
2020-02-05
Remark
内容要旨・審査要旨・論文本文の公開
本論文は,著者Ai Hanazakiの学位論文として提出され,学位審査・授与の対象となっている。
Rights
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.
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3346号
Diploma Number
甲栄第269号
Granted Date
2020-01-23
Degree Name
Doctor of Nutritional Science
Grantor
Tokushima University
departments
Medical Sciences