Compared with the well-described XY sex determination system in mammals, the avian ZW sex determination system is poorly understood. Knockdown and overexpression studies identified doublesex and mab-3-related transcription factor 1 (DMRT1) as the testis-determining gene in chicken. However, the detailed effects of DMRT1 gene disruption from embryonic to adult development are not clear. Herein, we have generated DMRT1-disrupted chickens using the clustered regularly interspaced short palindromic repeats-associated protein 9 system, followed by an analysis of physiological, hormonal, and molecular changes in the genome-modified chickens. In the early stages of male chicken development, disruption of DMRT1 induced gonad feminization with extensive physiological and molecular changes; however, functional feminine reproductivity could not be implemented with disturbed hormone synthesis. Subsequent RNA-sequencing analysis of the DMRT1-disrupted chicken gonads revealed gene networks, including several novel genes linearly and non-linearly associated with DMRT1, which are involved in gonad feminization. By comparing the gonads of wild type with the genome-modified chickens, a set of genes were identified that is involved in the ZW sex determination system independent of DMRT1. Our results extend beyond the Z-dosage hypothesis to provide further information about the avian ZW sex determination system and epigenetic effects of gonad feminization.

中文翻译：

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单独的 DMRT1 基因破坏诱导鸡性腺不完全雌性化

与哺乳动物中广为人知的 XY 性别决定系统相比，人们对鸟类 ZW 性别决定系统知之甚少。敲低和过表达研究将双性和 mab-3 相关转录因子 1 ( DMRT1 ) 鉴定为鸡的睾丸决定基因。然而， DMRT1基因破坏从胚胎到成人发育的详细影响尚不清楚。在此，我们使用成簇规律间隔的短回文重复序列相关蛋白 9 系统生成了DMRT1破坏的鸡，然后分析了基因组修饰鸡的生理、激素和分子变化。在雄性鸡发育的早期阶段，DMRT1的破坏诱导性腺女性化，具有广泛的生理和分子变化；然而，功能性女性生殖能力无法在激素合成受到干扰的情况下实现。随后对DMRT1破坏的鸡性腺进行的 RNA 测序分析揭示了基因网络，包括几个与DMRT1线性和非线性相关的新基因，它们参与性腺女性化。通过比较野生型与基因组修饰鸡的性腺，鉴定了一组独立于DMRT1参与 ZW 性别决定系统的基因。我们的结果超出了 Z 剂量假设，以提供有关禽类 ZW 性别决定系统和性腺女性化的表观遗传效应的更多信息。