Knockdown of bicaudal C in zebrafish (Danio rerio) causes cystic kidneys: a nonmammalian model of polycystic kidney disease.
Knockdown of bicaudal C in zebrafish (Danio rerio) causes cystic kidneys: a nonmammalian model of polycystic kidney disease.
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发表时间：
2010-04
影响因子：
0.8
通讯作者：
Denise J. Bouvrette;V. Sittaramane;J. Heidel;A. Chandrasekhar;E. Bryda
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作者：
Denise J. Bouvrette;V. Sittaramane;J. Heidel;A. Chandrasekhar;E. Bryda
多囊肾病（PKD）是人类终末期肾病的主要原因之一，其特征是进行性囊肿形成、肾脏肿大和肾小管发育异常。目前，多囊肾尚无治愈方法。尽管已经鉴定了许多 PKD 基因，但它们在囊肿发生中的确切作用仍不清楚。在 PKD 的 jcpk 小鼠模型中，双尾 C 基因 (Bicc1) 的突变导致了囊性表型；然而，Bicc1 的功能尚不清楚。在这项研究中，我们建立了另一种非哺乳动物斑马鱼模型来研究 Bicc1 在 PKD 发病机制中的作用。使用反义吗啉来评估斑马鱼 Bicc1 功能的丧失。对所得的变形体进行组织学检查以了解肾囊肿和结构异常。使用免疫染色和荧光染料注射来评估前肾纤毛和肾脏形态发生。斑马鱼 Bicc1 表达的敲低导致肾囊肿的形成；然而，没有观察到肾脏结构或前肾纤毛的缺陷。重要的是，小鼠 Bicc1 的表达挽救了 morphant 的囊性表型。这些结果表明 Bicc1 在肾脏中的功能在进化上是保守的，因此支持使用斑马鱼作为替代体内模型来研究哺乳动物 Bicc1 在肾囊肿形成中的作用。
Polycystic kidney disease (PKD) is one of the leading causes of end-stage renal disease in humans and is characterized by progressive cyst formation, renal enlargement, and abnormal tubular development. Currently, there is no cure for PKD. Although a number of PKD genes have been identified, their precise role in cystogenesis remains unclear. In the jcpk mouse model of PKD, mutations in the bicaudal C gene (Bicc1) are responsible for the cystic phenotype; however, the function of Bicc1 is unknown. In this study, we establish an alternative, nonmammalian zebrafish model to study the role of Bicc1 in PKD pathogenesis. Antisense morpholinos were used to evaluate loss of Bicc1 function in zebrafish. The resulting morphants were examined histologically for kidney cysts and structural abnormalities. Immunostaining and fluorescent dye injection were used to evaluate pronephric cilia and kidney morphogenesis. Knockdown of zebrafish Bicc1 expression resulted in the formation of kidney cysts; however, defects in kidney structure or pronephric cilia were not observed. Importantly, expression of mouse Bicc1 rescues the cystic phenotype of the morphants. These results demonstrate that the function of Bicc1 in the kidney is evolutionarily conserved, thus supporting the use of zebrafish as an alternative in vivo model to study the role of mammalian Bicc1 in renal cyst formation.