Pharmacological and Genetic Disruption of C-Type Natriuretic Peptide (nppcl) Expression in Zebrafish (Danio rerio) Causes Stunted Growth during Development.
Pharmacological and Genetic Disruption of C-Type Natriuretic Peptide (nppcl) Expression in Zebrafish (Danio rerio) Causes Stunted Growth during Development.
复制标题
C型利钠肽(Nppc1)在斑马鱼(Danio Rerio)中表达的药理和遗传干扰会导致发育迟缓。
DOI：
10.3390/ijms241612921
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发表时间：
2023-08-18
影响因子：
5.6
通讯作者：
Fowkes, Robert C.
中科院分区：
文献类型：
--
作者：
Lessey, Andrew J.;Mirczuk, Samantha M.;Chand, Annisa N.;Kurrasch, Deborah M.;Korbonits, Marta;Niessen, Stijn J. M.;Mcardle, Craig A.;Mcgonnell, Imelda M.;Fowkes, Robert C.
NPPC 或 NPR2 基因（分别编码 C 型利钠肽 (CNP) 和鸟苷酸环化酶-B (GC-B)）突变的人类患者表现出与骨骼异常相关的临床症状，例如过度生长或身材矮小。具有 Nppc 或 Npr2 缺失诱导模型的小鼠表现出严重的软骨发育不全、侏儒症和过早死亡。最近治疗身材矮小的药物疗法正在利用长效 CNP 类似物，但在发育过程中控制 CNP 表达的效果仍不清楚。在这里，我们使用斑马鱼作为脊椎动物发育的模型，采用药理学和反向遗传学方法来改变斑马鱼中编码 CNP 的基因的表达。在斑马鱼中鉴定出 CNP 的四种直系同源物，并且时空表达谱证实了它们在发育过程中的存在。生物信息学分析表明 nppcl 最有可能是哺乳动物 CNP 的直系同源物。外源性 CNP 处理发育中的斑马鱼胚胎会导致生长特性受损，例如体长、头宽和眼睛直径。这种生长减少可能是由 CNP 治疗后细胞凋亡增加引起的。在这些 CNP 处理的胚胎中，内源性 nppcl 的表达下调，表明 CNP 系统的负反馈可能会影响发育过程中的生长。 CRISPR 敲低斑马鱼胚胎发育中的内源性 nppcl 也会导致生长特性受损。总的来说，这些数据表明斑马鱼的 CNP 对于正常胚胎发育至关重要，特别是在生长方面。
Human patients with mutations within NPPC or NPR2 genes (encoding C-type natriuretic peptide (CNP) and guanylyl cyclase-B (GC-B), respectively) display clinical signs associated with skeletal abnormalities, such as overgrowth or short stature. Mice with induced models of Nppc or Npr2 deletion display profound achondroplasia, dwarfism and early death. Recent pharmacological therapies to treat short stature are utilizing long-acting CNP analogues, but the effects of manipulating CNP expression during development remain unknown. Here, we use Danio rerio (zebrafish) as a model for vertebrate development, employing both pharmacological and reverse genetics approaches to alter expression of genes encoding CNP in zebrafish. Four orthologues of CNP were identified in zebrafish, and spatiotemporal expression profiling confirmed their presence during development. Bioinformatic analyses suggested that nppcl is the most likely the orthologue of mammalian CNP. Exogenous CNP treatment of developing zebrafish embryos resulted in impaired growth characteristics, such as body length, head width and eye diameter. This reduced growth was potentially caused by increased apoptosis following CNP treatment. Expression of endogenous nppcl was downregulated in these CNP-treated embryos, suggesting that negative feedback of the CNP system might influence growth during development. CRISPR knock-down of endogenous nppcl in developing zebrafish embryos also resulted in impaired growth characteristics. Collectively, these data suggest that CNP in zebrafish is crucial for normal embryonic development, specifically with regard to growth.
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影响因子：
16.6
作者：
Estrada K;Froelich S;Wuster A;Bauer CR;Sterling T;Clark WT;Ru Y;Trinidad M;Nguyen HP;Luu AR;Wendt DJ;Yogalingam G;Yu GK;LeBowitz JH;Cardon LR
通讯作者：
Cardon LR
影响因子：
3.7
作者：
Hirota K;Furuya M;Morozumi N;Yoshikiyo K;Yotsumoto T;Jindo T;Nakamura R;Murakami K;Ueda Y;Hanada T;Sade H;Yoshida S;Enomoto K;Kanai Y;Yamauchi I;Yamashita T;Ueda-Sakane Y;Fujii T;Yasoda A;Inagaki N
通讯作者：
Inagaki N
C 型利钠肽/利钠肽受体 2 参与小鼠间质细胞的细胞增殖和睾酮生成
DOI：
10.5534/wjmh.180041
发表时间：
2019-05
期刊：
The world journal of men's health
影响因子：
--
作者：
Yang L;Lei L;Zhao Q;Gong Y;Guan G;Huang S
通讯作者：
Huang S
DOI：
10.1073/pnas.1632368100
发表时间：
2003-08-19
影响因子：
11.1
作者：
Inoue, K;Naruse, K;Takei, Y
通讯作者：
Takei, Y
影响因子：
4
作者：
Fowkes, RC;Forrest-Owen, W;McArdle, CA
通讯作者：
McArdle, CA