Sexual dimorphisms are prevalent in development, physiology and diseases in humans. Currently, the contributions of the genes on the male-specific region of the Y chromosome (MSY) in these processes are uncertain. Using a transgene activation system, the human sex-determining gene hSRY is activated in the single-cell embryos of the mouse. Pups with hSRY activated (hSRYON) are born of similar sizes as those of non-activated controls. However, they retard significantly in postnatal growth and development and all die of multi-organ failure before two weeks of age. Pathological and molecular analyses indicate that hSRYON pups lack innate suckling activities, and develop fatty liver disease, arrested alveologenesis in the lung, impaired neurogenesis in the brain and occasional myocardial fibrosis and minimized thymus development. Transcriptome analysis shows that, in addition to those unique to the respective organs, various cell growth and survival pathways and functions are differentially affected in the transgenic mice. These observations suggest that ectopic activation of a Y-located SRY gene could exert male-specific effects in development and physiology of multiple organs, thereby contributing to sexual dimorphisms in normal biological functions and disease processes in affected individuals.

译文

性双态性在人类的发育,生理和疾病中普遍存在。目前,这些过程中Y染色体(MSY)的男性特定区域上的基因贡献尚不确定。使用转基因激活系统,人类性别决定基因hSRY在小鼠的单细胞胚胎中被激活。激活了hSRY的幼犬(hSRYON)的大小与未激活的对照相似。然而,它们在出生后的生长和发育中显着地延迟,并且在两周龄之前都死于多器官衰竭。病理和分子分析表明,hSRYON幼崽缺乏先天的哺乳活动,并发展为脂肪肝疾病,阻止了肺中的肺泡形成,大脑中的神经发生受损以及偶发的心肌纤维化,并使胸腺的发育减至最小。转录组分析表明,除了各个器官特有的那些外,转基因小鼠中各种细胞的生长,存活途径和功能也受到不同的影响。这些观察结果表明,异位激活Y-定位的SRY基因可以在多个器官的发育和生理中发挥雄性特异性作用,从而在受影响个体的正常生物学功能和疾病过程中促成性二态性。

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