Rats deficient C-type natriuretic peptide suffer from impaired skeletal growth without early death.
Rats deficient C-type natriuretic peptide suffer from impaired skeletal growth without early death.
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DOI：
10.1371/journal.pone.0194812
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Nakao K
中科院分区：
文献类型：
--
作者：
Fujii T;Hirota K;Yasoda A;Takizawa A;Morozumi N;Nakamura R;Yotsumoto T;Kondo E;Yamashita Y;Sakane Y;Kanai Y;Ueda Y;Yamauchi I;Yamanaka S;Nakao K;Kuwahara K;Jindo T;Furuya M;Mashimo T;Inagaki N;Serikawa T;Nakao K
我们以前研究了C型利钠肽（CNP）对软骨内骨生长的生理作用，主要是用CNP缺陷的突变小鼠模型，并报道CNP是小鼠生理性软骨内骨生长不可缺少的。然而，CNP敲除（KO）小鼠的存活率下降到低至约70%，直到出生后10周，我们无法充分分析成年阶段的表型。在此，我们通过使用锌指核酸酶介导的基因组编辑技术产生CNP KO大鼠。我们建立了两种CNP完全缺陷的突变大鼠（CNP KO大鼠），其表现出与CNP缺陷小鼠相同的表型，即身材矮小伴软骨内骨生长严重受损。组织学分析显示，CNP KO大鼠生长板的宽度，特别是肥大软骨细胞层的宽度明显降低，生长板软骨细胞的增殖趋于减少。值得注意的是，CNP KO大鼠没有咬合不正，并且在出生后存活超过一年。在33周龄时，CNP KO大鼠的持续时间显著短于野生型大鼠，所有样品中股骨生长板闭合，而野生型大鼠中未观察到。在组织学上，CNP缺乏症仅影响研究的所有身体组织中的骨骼。因此，CNP KO大鼠存活超过1年，并在整个生命期内表现出软骨内骨生长缺陷和生长迟缓。
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.
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DOI：
10.1073/pnas.0510019103
发表时间：
2006-03-21
影响因子：
11.1
作者：
Langenickel, TH;Buttgereit, J;Bader, M
通讯作者：
Bader, M
影响因子：
3.9
作者：
Bocciardi, Renata;Giorda, Roberto;Gimellio, Giorgio
通讯作者：
Gimellio, Giorgio
影响因子：
5.8
作者：
Olney, RC;Bükülmez, H;Warman, ML
通讯作者：
Warman, ML
影响因子：
5.8
作者：
Hachiya, Rumi;Ohashi, Yuko;Ogawa, Yoshihiro
通讯作者：
Ogawa, Yoshihiro
DOI：
10.1126/science.1172447
发表时间：
2009-07-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Geurts AM;Cost GJ;Freyvert Y;Zeitler B;Miller JC;Choi VM;Jenkins SS;Wood A;Cui X;Meng X;Vincent A;Lam S;Michalkiewicz M;Schilling R;Foeckler J;Kalloway S;Weiler H;Ménoret S;Anegon I;Davis GD;Zhang L;Rebar EJ;Gregory PD;Urnov FD;Jacob HJ;Buelow R
通讯作者：
Buelow R