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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 humans, 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, goiter and, infertility. Homozygous mutants in adults also displayed extrathyroidal 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 2 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.<\/jats:p>","DOI":"10.1210\/endocr\/bqab101","type":"journal-article","created":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T20:37:33Z","timestamp":1621629453000},"source":"Crossref","is-referenced-by-count":11,"title":["Genetic Manipulation on Zebrafish <i>duox<\/i> Recapitulate the Clinical Manifestations of Congenital Hypothyroidism"],"prefix":"10.1210","volume":"162","author":[{"given":"Feng","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Molecular Diagnostics and Endocrinology, The Core Laboratory in Medical Center of Clinical Research, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnostics and Endocrinology, The Core Laboratory in Medical Center of Clinical Research, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man-Man","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnostics and Endocrinology, The Core Laboratory in Medical Center of Clinical Research, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Jia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnostics and Endocrinology, The Core Laboratory in Medical Center of Clinical Research, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Yao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnostics and Endocrinology, The Core Laboratory in Medical Center of Clinical Research, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Meng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnostics and Endocrinology, The Core Laboratory in Medical Center of Clinical Research, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping-Hui","family":"Tu","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnostics and Endocrinology, The Core Laboratory in Medical Center of Clinical Research, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnostics and Endocrinology, The Core Laboratory in Medical Center of Clinical Research, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5015-9541","authenticated-orcid":false,"given":"Shuang-Xia","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnostics and Endocrinology, The Core Laboratory in Medical Center of Clinical Research, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9609-5803","authenticated-orcid":false,"given":"Huai-Dong","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnostics and Endocrinology, The Core Laboratory in Medical Center of Clinical Research, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2021,5,21]]},"reference":[{"issue":"5","key":"2021121717583749900_CIT0001","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1136\/jmg.2004.024158","article-title":"Genetics of congenital hypothyroidism","volume":"42","author":"Park","year":"2005","journal-title":"J Med Genet."},{"issue":"8","key":"2021121717583749900_CIT0002","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1210\/jc.2011-1073","article-title":"Is the incidence of congenital hypothyroidism really increasing? A 20-year retrospective population-based study in Qu\u00e9bec","volume":"96","author":"Delado\u00eby","year":"2011","journal-title":"J Clin Endocrinol Metab."},{"issue":"8","key":"2021121717583749900_CIT0003","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1210\/jc.2011-1850","article-title":"Increasing incidence of congenital hypothyroidism: some answers, more questions","volume":"96","author":"LaFranchi","year":"2011","journal-title":"J Clin Endocrinol Metab."},{"key":"2021121717583749900_CIT0004","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1750-1172-5-17","article-title":"Congenital hypothyroidism","volume":"5","author":"Rastogi","year":"2010","journal-title":"Orphanet J Rare Dis."},{"issue":"4","key":"2021121717583749900_CIT0005","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1097\/MOP.0b013e32834726a4","article-title":"Genetic causes of congenital hypothyroidism due to dyshormonogenesis","volume":"23","author":"Grasberger","year":"2011","journal-title":"Curr Opin Pediatr."},{"issue":"6","key":"2021121717583749900_CIT0006","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1530\/EJE-17-1017","article-title":"The genetic characteristics of congenital hypothyroidism in China by comprehensive screening of 21 candidate genes","volume":"178","author":"Sun","year":"2018","journal-title":"Eur J Endocrinol."},{"issue":"52","key":"2021121717583749900_CIT0007","doi-asserted-by":"crossref","first-page":"37265","DOI":"10.1074\/jbc.274.52.37265","article-title":"Purification of a novel flavoprotein involved in the thyroid NADPH oxidase. 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