Mutation of foxl2 or cyp19a1a Results in Female to Male Sex Reversal in XX Nile Tilapia
Mutation of foxl2 or cyp19a1a Results in Female to Male Sex Reversal in XX Nile Tilapia
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Foxl2或cyp19a1a突变导致XX尼罗罗非鱼雌性向雄性逆转
DOI：
10.1210/en.2017-00127
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发表时间：
2017-08
期刊：
影响因子：
4.8
通讯作者：
Wang Deshou
中科院分区：
文献类型：
--
作者：
Zhang Xianbo;Li Mengru;Ma He;Liu Xingyong;Shi Hongjuan;Li Minghui;Wang Deshou
叉头盒蛋白L2（Foxl 2）和芳香化酶（Cyp 19 a1;负责雌激素合成的酶）对脊椎动物的卵巢发育至关重要。山羊、小鼠和斑马鱼中Foxl 2和Cyp 19 a1的敲除揭示了物种间相似但不相同的功能。这两个基因在其他动物中的功能分析是必要的，以阐明它们在脊椎动物性发育中的保守作用。在本研究中，我们建立了尼罗罗非鱼foxl 2和cyp 19 a1 a突变系。fox 12-/-和cyp 19 a1 a-/- XX鱼都表现出雌性到雄性的性逆转。Sf 1、Dmrt 1和Gsdf在foxl 2-/-和cyp 19 a1 a-/- XX性腺中上调。在foxl 2-/- XX鱼中观察到Cyp 19 a1 a和血清雌二醇-17 β水平下调，Cyp 11b 2和血清11-酮睾酮水平上调。17β-雌二醇在孵化后5 ~ 30天处理fox 12-/- XX个体，可挽救突变表型。在30和90 dah时，在foxl 2-/- XX性腺中也观察到Star 1（罗非鱼雄激素产生中涉及的酶）的上调。体外启动子分析一致表明，Foxl 2可以抑制转录的star 1在剂量依赖性的方式。此外，与对照XX性腺相比，在foxl 2-/- XX、cyp 19 a1 a-/- XX和对照XY性腺中检测到较少的生殖细胞。这些结果表明，Foxl 2通过上调Cyp 19 a1 a表达和抑制雄性途径基因表达来促进卵巢发育。这些结果将Foxl 2和Cyp 19 a1 a功能丧失的研究扩展到商业上重要的鱼类物种。
It is well accepted that Forkhead box protein L2 (Foxl2) and aromatase (Cyp19a1; the enzyme responsible for estrogen synthesis) are critical for ovarian development in vertebrates. Knockouts of Foxl2 and Cyp19a1 in goat, mouse, and zebrafish have revealed similar but not identical functions across species. Functional analyses of these two genes in other animals are needed to elucidate their conserved roles in vertebrate sexual development. In this study, we established foxl2 and cyp19a1a mutant lines in Nile tilapia. Both foxl2-/- and cyp19a1a-/- XX fish displayed female-to-male sex reversal. Sf1, Dmrt1, and Gsdf were upregulated in the foxl2-/- and the cyp19a1a-/- XX gonads. Downregulation of Cyp19a1a and serum estradiol-17β level, and upregulation of Cyp11b2 and serum 11-ketotestosterone level were observed in foxl2-/- XX fish. The mutant phenotype of foxl2-/- XX individuals could be rescued by 17β-estradiol treatment from 5 to 30 days after hatching (dah). Upregulation of Star1, the enzyme involved in androgen production in tilapia, was also observed in the foxl2-/- XX gonad at 30 and 90 dah. In vitro promoter analyses consistently demonstrated that Foxl2 could suppress the transcription of star1 in a dose-dependent manner. In addition, compared with the control XX gonad, fewer germ cells were detected in the foxl2-/- XX, cyp19a1a-/- XX, and control XY gonads 10 dah. These results demonstrate that Foxl2 promotes ovarian development by upregulating Cyp19a1a expression and repressing male pathway gene expression. These results extend the study of Foxl2 and Cyp19a1a loss of function to a commercially important fish species.
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影响因子：
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作者：
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DOI：
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发表时间：
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影响因子：
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