DMRT1 gene disruption alone induces incomplete gonad feminization in chicken.
DMRT1 gene disruption alone induces incomplete gonad feminization in chicken.
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DMRT1基因破坏仅会诱导鸡的性腺女性化不完全。
DOI：
10.1096/fj.202100902r
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发表时间：
2021-09
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与哺乳动物的XY性别决定系统相比，对鸟类的ZW性别决定系统了解甚少。敲除和过表达研究确定doublexandmab 3相关转录因子1（DMRT 1）为鸡睾丸决定基因。然而，DMRT 1基因从胚胎到成体发育的详细影响尚不清楚。在本文中，我们使用成簇规则间隔短回文重复序列（CRISPR）相关蛋白9（CRISPR/Cas9）系统产生了DMRT 1破坏的鸡，然后分析了基因组修饰的鸡的生理，激素和分子变化。在雄鸡发育的早期阶段，DMRT 1的破坏诱导性腺雌性化与广泛的生理和分子变化;然而，功能性雌性生殖不能实施干扰激素合成。随后对DMRT 1破坏的鸡性腺进行的RNA测序分析揭示了基因网络，包括与DMRT 1线性和非线性相关的几个新基因，这些基因参与性腺雌性化。通过比较野生型和基因组修饰的鸡的性腺，鉴定出一组独立于DMRT 1参与ZW性别决定系统的基因。我们的结果超出了Z剂量假设，提供了有关鸟类ZW性别决定系统和性腺雌性化的表观遗传效应的进一步信息。
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 (CRISPR)-associated protein 9 (CRISPR/Cas9) 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.