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Title: Rats deficient C-type natriuretic peptide suffer from impaired skeletal growth without early death
Authors: Fujii, Toshihito
Hirota, Keisho
Yasoda, Akihiro  kyouindb  KAKEN_id
Takizawa, Akiko
Morozumi, Naomi
Nakamura, Ryuichi
Yotsumoto, Takafumi
Kondo, Eri
Yamashita, Yui
Sakane, Yoriko
Kanai, Yugo
Ueda, Yohei
Yamauchi, Ichiro
Yamanaka, Shigeki
Nakao, Kazumasa  kyouindb  KAKEN_id
Kuwahara, Koichiro
Jindo, Toshimasa
Furuya, Mayumi
Mashimo, Tomoji
Inagaki, Nobuya
Serikawa, Tadao
Nakao, Kazuwa
Author's alias: 藤井, 寿人
八十田, 明宏
坂根, 依利子
山中, 茂樹
中尾, 一祐
稲垣, 暢也
中尾, 一和
Issue Date: 22-Mar-2018
Publisher: Public Library of Science (PLoS)
Journal title: PLOS ONE
Volume: 13
Issue: 3
Start page: e0194812
Abstract: We have previously investigated the physiological role of C-type natriuretic peptide (CNP) on endochondral bone growth, mainly with mutant mouse models deficient in CNP, and reported that CNP is indispensable for physiological endochondral bone growth in mice. However, the survival rate of CNP knockout (KO) mice fell to as low as about 70% until 10 weeks after birth, and we could not sufficiently analyze the phenotype at the adult stage. Herein, we generated CNP KO rats by using zinc-finger nuclease-mediated genome editing technology. We established two lines of mutant rats completely deficient in CNP (CNP KO rats) that exhibited a phenotype identical to that observed in mice deficient in CNP, namely, a short stature with severely impaired endochondral bone growth. Histological analysis revealed that the width of the growth plate, especially that of the hypertrophic chondrocyte layer, was markedly lower and the proliferation of growth plate chondrocytes tended to be reduced in CNP KO rats. Notably, CNP KO rats did not have malocclusions and survived for over one year after birth. At 33 weeks of age, CNP KO rats persisted significantly shorter than wild-type rats, with closed growth plates of the femur in all samples, which were not observed in wild-type rats. Histologically, CNP deficiency affected only bones among all body tissues studied. Thus, CNP KO rats survive over one year, and exhibit a deficit in endochondral bone growth and growth retardation throughout life.
Rights: © 2018 Fujii et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
URI: http://hdl.handle.net/2433/231086
DOI(Published Version): 10.1371/journal.pone.0194812
PubMed ID: 29566041
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