Genetic Manipulation on Zebrafish duox Recapitulate the Clinical Manifestations of Congenital Hypothyroidism.

May 24, 2021

Contributor: Feng Sun,Ya Fang,Man-Man Zhang,Rui-Jia Zhang,Feng-Yao Wu,Rui-Meng Yang,Ping-Hui Tu,Mei Dong,Shuang-Xia Zhao,Huai-Dong Song

Genetic Manipulation on Zebrafish duox Recapitulate the Clinical Manifestations of Congenital Hypothyroidism.

Congenital hypothyroidism (CH) is a highly prevalent but treatable neonatal endocrine disorder. Thyroid dyshormonogenesis is the main cause of congenital hypothyroidism in Chinese CH patients and DUOX2 is the most frequent mutated gene involved in H2O2 production. In human, the primary sources for H2O2 production are DUOX1 and DUOX2, while in zebrafish, there is only a single orthologue for DUOX1 and DUOX2. In this study, duox mutant zebrafish were generated through knockdown duox by morpholino or knockout duox by CRISPR Cas9. The associated phenotypes were investigated and rescued by thyroxine (T4) treatment. Mutant zebrafish displayed hypothyroid phenotypes including growth retardation and goiter and infertility. Homozygous mutants in adults also displayed extra-thyroidal abnormal phenotypes including lacking barbels, pigmentation defects, erythema in the opercular region, ragged fins and delayed scales. All these abnormal phenotypes can be rescued by 10 nM T4 treatment. Strikingly, the fertility of zebrafish was dependent on thyroid hormone, T4 treatment should be continued and cannot be stopped over two weeks in hypothyroid zebrafish in order to achieve fertility. Thyroid hormones played a role in the developing and maturing of reproductive cells. Our work indicated that duox mutant zebrafish may provide a model for human congenital hypothyroidism.
© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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About The Expert

Feng Sun

Department of Molecular Diagnostics, The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People’s Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Ya Fang

Department of Molecular Diagnostics, The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People’s Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Man-Man Zhang

Department of Molecular Diagnostics, The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People’s Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Rui-Jia Zhang

Department of Molecular Diagnostics, The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People’s Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Feng-Yao Wu

Department of Molecular Diagnostics, The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People’s Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Rui-Meng Yang

Department of Molecular Diagnostics, The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People’s Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Ping-Hui Tu

Department of Molecular Diagnostics, The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People’s Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Mei Dong

Department of Molecular Diagnostics, The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People’s Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Shuang-Xia Zhao

Department of Molecular Diagnostics, The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People’s Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Huai-Dong Song

Department of Molecular Diagnostics, The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People’s Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

References

PubMed