斑马鱼<italic style="font-style: italic">cdt1</italic>缺失导致类似人类Meier-Gorlin疾病的侏儒症及性腺发育不全综合征

何一囡; 王勇; 祝岩清; 罗丽健

doi:10.1631/jzus.B2300195

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斑马鱼cdt1缺失导致类似人类Meier-Gorlin疾病的侏儒症及性腺发育不全综合征

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Correspondence | Updated：2023-11-15

斑马鱼cdt1缺失导致类似人类Meier-Gorlin疾病的侏儒症及性腺发育不全综合征
Loss-of-function of zebrafish cdt1 causes retarded body growth and underdeveloped gonads resembling human Meier-Gorlin syndrome
浙江大学学报（英文版）（B辑：生物医学和生物技术） 2023年24卷第11期页码：1037-1046
Affiliations：

1.MOE Key Laboratory for Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China
2.Pathology Department of Taizhou Hospital, Zhejiang University, Taizhou 317000, China
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DOI：10.1631/jzus.B2300195
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何一囡,王勇,祝岩清等.斑马鱼cdt1缺失导致类似人类Meier-Gorlin疾病的侏儒症及性腺发育不全综合征[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2023,24(11):1037-1046.

Yinan HE, Yong WANG, Yanqing ZHU, et al. Loss-of-function of zebrafish cdt1 causes retarded body growth and underdeveloped gonads resembling human Meier-Gorlin syndrome[J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2023,24(11):1037-1046.
何一囡,王勇,祝岩清等.斑马鱼cdt1缺失导致类似人类Meier-Gorlin疾病的侏儒症及性腺发育不全综合征[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2023,24(11):1037-1046. DOI： 10.1631/jzus.B2300195.

Yinan HE, Yong WANG, Yanqing ZHU, et al. Loss-of-function of zebrafish cdt1 causes retarded body growth and underdeveloped gonads resembling human Meier-Gorlin syndrome[J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2023,24(11):1037-1046. DOI： 10.1631/jzus.B2300195.

摘要

Abstract

染色质许可和DNA复制因子1（Cdt1）是复制起始许可的主要调控因子，也是组成复制前复合物的核心成员。细胞通过依赖Cdt1的波动水平，且在每个周期中通过调节其总量以确保DNA仅复制一次。Cdt1功能缺陷会造成DNA过度复制，最终导致基因组不稳定。虽然酵母中,cdt1,和人类Meier-Gorlin综合征（MGS）患者中的,CDT1,已被广泛研究，但缺乏脊椎动物模型。我们发现在硬骨鱼类分支的几个鲤形目物种（包括斑马鱼）中，Cdt1蛋白在其N末端插入一段其他脊椎动物中没有的独特无序序列。通过分析在,cdt1,基因中携带移码缺失的遗传性斑马鱼突变体（命名为,cdt1,zju1,），我们发现突变胚胎虽然几乎无任何早期胚胎表型异常，但成年突变斑马鱼却表现出侏儒症、生存能力降低的症状，以及性腺发育不全且不育。此外，我们同样发现除转录本,cdt1-201,外，斑马鱼还存在第二个,cdt1,转录本——,cdt1-202,，它是通过跳过外显子2产生，这在其他生物中暂无报道。有意思的是,cdt1-202,在,cdt1-201,纯合突变体中显著上调。上述研究结果表明，,cdt1-202,转录本可能可以补偿,cdt1-201,在早期发育过程中的功能损失，但不能补偿后期生长，这可支持斑马鱼作为研究人类MGS的遗传模型。

关键词

斑马鱼N端序列cdt1-201cdt1-202侏儒症不育

Keywords

references

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斑马鱼cdt1缺失导致类似人类Meier-Gorlin疾病的侏儒症及性腺发育不全综合征

Loss-of-function of zebrafish cdt1 causes retarded body growth and underdeveloped gonads resembling human Meier-Gorlin syndrome

DOI：10.1631/jzus.B2300195

摘要

Abstract

关键词

Keywords

references