Loss-of-function of zebrafish <italic style="font-style: italic">cdt1</italic> causes retarded body growth and underdeveloped gonads resembling human Meier-Gorlin syndrome

Yinan HE; Yong WANG; Yanqing ZHU; Li Jan LO

doi:10.1631/jzus.B2300195

Your Location：

Home >

Browse articles >

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

Scan for full text

Alert me when the article has been cited

Submit

Correspondence | Updated：2023-11-15

Loss-of-function of zebrafish cdt1 causes retarded body growth and underdeveloped gonads resembling human Meier-Gorlin syndrome
Loss-of-function of zebrafish cdt1 causes retarded body growth and underdeveloped gonads resembling human Meier-Gorlin syndrome
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
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) Vol. 24, Issue 11, Pages: 1037-1046(2023)
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
Funds：
DOI：10.1631/jzus.B2300195
CLC：
CSTR：

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) 24(11):1037-1046(2023)
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) 24(11):1037-1046(2023) 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

Alfa CE, Booher R, Beach D, et al., 1989. Fission yeast cyclin: subcellular localisation and cell cycle regulation. J Cell Sci, 1989(S12):9-19. https://doi.org/10.1242/jcs.1989.supplement_12.2https://doi.org/10.1242/jcs.1989.supplement_12.2

Bicknell LS, Walker S, Klingseisen A, et al., 2011. Mutations in ORC1, encoding the largest subunit of the origin recognition complex, cause microcephalic primordial dwarfism resembling Meier-Gorlin syndrome. Nat Genet, 43(4):350-355. https://doi.org/10.1038/ng.776https://doi.org/10.1038/ng.776

de Munnik SA, Hoefsloot EH, Roukema J, et al., 2015. Meier-Gorlin syndrome. Orphanet J Rare Dis, 10:114. https://doi.org/10.1186/s13023-015-0322-xhttps://doi.org/10.1186/s13023-015-0322-x

Hofmann JF, Beach D, 1994. cdt1 is an essential target of the Cdc10/Sct1 transcription factor: requirement for DNA replication and inhibition of mitosis. EMBO J, 13‍(2):425-434. https://doi.org/10.1002/j.1460-2075.1994.tb06277.xhttps://doi.org/10.1002/j.1460-2075.1994.tb06277.x

Kanellou A, Giakoumakis NN, Panagopoulos A, et al., 2020. The licensing factor Cdt1 links cell cycle progression to the DNA damage response. Anticancer Res, 40(5):2449-2456. https://doi.org/10.21873/anticanres.14214https://doi.org/10.21873/anticanres.14214

Ma ZP, Zhu PP, Shi H, et al., 2019. PTC-bearing mRNA elicits a genetic compensation response via Upf3a and COMPASS components. Nature, 568(7751):259-263. https://doi.org/10.1038/s41586-019-1057-yhttps://doi.org/10.1038/s41586-019-1057-y

Maiorano D, Moreau J, Méchali M, 2000. XCDT1 is required for the assembly of pre-replicative complexes in Xenopus laevis. Nature, 404(6778):622-625. https://doi.org/10.1038/35007104https://doi.org/10.1038/35007104

Nazarenko MS, Viakhireva IV, Skoblov MY, et al., 2022. Meier-Gorlin syndrome: clinical misdiagnosis, genetic testing and functional analysis of ORC6 mutations and the development of a prenatal test. Int J Mol Sci, 23(16):9234. https://doi.org/10.3390/ijms23169234https://doi.org/10.3390/ijms23169234

Nishitani H, Lygerou Z, Nishimoto T, et al., 2000. The Cdt1 protein is required to license DNA for replication in fission yeast. Nature, 404(6778):625-628. https://doi.org/10.1038/35007110https://doi.org/10.1038/35007110

Pozo PN, Cook JG, 2017. Regulation and function of Cdt1; a key factor in cell proliferation and genome stability. Genes (Basel), 8(1):2. https://doi.org/10.3390/genes8010002https://doi.org/10.3390/genes8010002

Vaziri C, Saxena S, Jeon Y, et al., 2003. A p53-dependent checkpoint pathway prevents rereplication. Mol Cell, 11(4):997-1008. https://doi.org/10.1016/s1097-2765(03)00099-6https://doi.org/10.1016/s1097-2765(03)00099-6

Whittaker AJ, Royzman I, Orr-Weaver TL, 2000. Drosophila Double parked: a conserved, essential replication protein that colocalizes with the origin recognition complex and links DNA replication with mitosis and the down-regulation of S phase transcripts. Genes Dev, 14(14):1765-1776. https://doi.org/10.1101/gad.14.14.1765https://doi.org/10.1101/gad.14.14.1765

Wittkopp N, Huntzinger E, Weiler C, et al., 2009. Nonsense-mediated mRNA decay effectors are essential for zebrafish embryonic development and survival. Mol Cell Biol, 29(13):3517-3528. https://doi.org/10.1128/MCB.00177-09https://doi.org/10.1128/MCB.00177-09

Wohlschlegel JA, Dwyer BT, Dhar SK, et al., 2000. Inhibition of eukaryotic DNA replication by geminin binding to Cdt1. Science, 290(5500):2309-2312. https://doi.org/10.1126/science.290.5500.2309https://doi.org/10.1126/science.290.5500.2309

Yao LK, Chen J, Wu XT, et al., 2017. Zebrafish cdc6 hypomorphic mutation causes Meier-Gorlin syndrome-like phenotype. Hum Mol Genet, 26(21):4168-4180. https://doi.org/10.1093/hmg/ddx305https://doi.org/10.1093/hmg/ddx305

Views

Downloads

CSCD

Tools

Publicity Resources

No data

Related Author

No data

Related Institution

No data

Address：Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou, China Postal code：310027
Tel：+86-571-87952783 Email：cjzhang@zju.edu.cn
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备09064830号-19 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰

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

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