nr0b1 (DAX1) mutation in zebrafish causes female-to-male sex reversal through abnormal gonadal proliferation and differentiation
nr0b1 (DAX1) mutation in zebrafish causes female-to-male sex reversal through abnormal gonadal proliferation and differentiation
复制标题
斑马鱼的 nr0b1 (DAX1) 突变通过异常的性腺增殖和分化导致雌性向雄性的性别逆转。
DOI：
10.1016/j.mce.2016.06.005
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发表时间：
2016-09-15
影响因子：
4.1
通讯作者：
Peng, Gang
中科院分区：
文献类型：
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作者：
Chen, Sijie;Zhang, Hefei;Peng, Gang
脊椎动物的性别决定是多样的。尽管许多性别决定基因和通路是保守的，但这些基因和通路在遗传性别决定中的机制作用尚未得到很好的理解。DAX1（由NR0B1基因编码）是一种脊椎动物特有的孤儿核受体，它调节性腺发育和性别决定。在人类中，NR0B1基因的重复会导致男性向女性的性别反转。在小鼠中，Nr0b1表现出促睾丸和抗睾丸两种功能。我们在斑马鱼中产生了可遗传的nr0b1突变，发现nr0b1突变导致纯合突变体由于雌性向雄性的性别反转而发育为可育的雄性。nr0b1突变并没有增加发育中的性腺中Caspase - 3标记或tp53表达。将tp53突变引入nr0b1突变体中并没有挽救性别反转表型。进一步的检查显示，在未分化和双潜能卵巢阶段，nr0b1突变体性腺中的细胞增殖减少和体细胞分化异常。总之，我们的结果表明nr0b1调节体细胞分化和细胞增殖，以确保斑马鱼的正常性别发育。（C）2016爱思唯尔爱尔兰有限公司。保留所有权利。
Sex determinations are diverse in vertebrates. Although many sex-determining genes and pathways are conserved, the mechanistic roles of these genes and pathways in the genetic sex determination are not well understood. DAX1 (encoded by the NR0B1 gene) is a vertebrate specific orphan nuclear receptor that regulates gonadal development and sexual determination. In human, duplication of the NR0B1 gene leads to male-to-female sex reversal. In mice, Nr0b1 shows both pro-testis and anti -testis functions. We generated inheritable nr0b1 mutation in the zebrafish and found the nr0b1 mutation caused homozygous mutants to develop as fertile males due to female-to-male sex reversal. The nr0b1 mutation did not increase Caspase-3 labeling nor tp53 expression in the developing gonads. Introduction of a tp53 mutation into the nr0b1 mutant did not rescue the sex-reversal phenotype. Further examination revealed reduction in cell proliferation and abnormal somatic cell differentiation in the nr0b1 mutant gonads at the undifferentiated and bi-potential ovary stages. Together, our results suggest nr0b1 regulates somatic cell differentiation and cell proliferation to ensure normal sex development in the zebrafish. (C) 2016 Elsevier Ireland Ltd. All rights reserved.