The androgen receptor (AR) is known for masculinization of behavior and brain. To better understand the role that AR plays, mice bearing humanized Ar genes with varying lengths of a polymorphic N-terminal glutamine (Q) tract were created (Albertelli et al 2006). The length of the Q tract is inversely proporitional to AR activity. Biological studies of the Q tract length may also provide a window into potential AR contributions to sex-biases in disease risk. Here we take a multi-pronged approach to characterizing AR signaling effects on brain and behavior in mice using the humanized Ar Q tract model. We first map effects of Q tract length on regional brain anatomy, and consider if these are modified by gonadal sex. We then test the notion that spatial patterns of anatomical variation related to Q tract length could be organized by intrinsic spatiotemporal patterning of AR gene expression in the mouse brain. Finally, we test influences of Q tract length on four behavioral tests. Altering Q tract length led to neuroanatomical differences in a non-linear dosage-dependent fashion. Gene expression analyses indicated that adult neu- roanatomical changes due to Q tract length are only associated with neurode- velopment (as opposed to adulthood). No significant effect of Q tract length was found on the behavior of the three mouse models. These results indicate that AR activity differentially mediates neuroanatomy and behavior, that AR activity alone does not mediate sex differences, and that neurodevelopmen- tal processes are associated with spatial patterns of volume changes due to Q tract length in adulthood. They also indicate that androgen sensitivity in adulthood is not likely to lead to autism-related behaviors or neuroanatomy, although neurodevelopmental processes may play a role earlier. Further study into sex differences, development, other behaviors, and other sex-specific mech- anisms are needed to better understand AR sensitivity, neurodevelopmental disorders, and the sex difference in their prevalence.

中文翻译：

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具有不同多态性长度的人源化雄激素受体基因 (h/mAr) 的小鼠的表征

雄激素受体 (AR) 以行为和大脑的男性化而闻名。为了更好地了解 AR 所起的作用，我们创建了携带具有不同长度的多态性 N 末端谷氨酰胺 (Q) 束的人源化 Ar 基因的小鼠 (Albertelli et al 2006)。Q 束的长度与 AR 活动成反比。Q 束长度的生物学研究也可能为了解 AR 对疾病风险中的性别偏见的潜在贡献提供了一个窗口。在这里，我们采用多管齐下的方法来使用人性化的 Ar Q 束模型来表征 AR 信号对小鼠大脑和行为的影响。我们首先绘制 Q 束长度对局部大脑解剖结构的影响，并考虑这些是否被性腺性改变。然后，我们测试了与 Q 束长度相关的解剖变异的空间模式可以通过小鼠大脑中 AR 基因表达的内在时空模式来组织的概念。最后，我们测试了 Q 束长度对四个行为测试的影响。改变 Q 束长度以非线性剂量依赖性方式导致神经解剖学差异。基因表达分析表明，由于 Q 束长度引起的成人神经解剖学变化仅与神经发育相关（与成年期相反）。没有发现 Q 束长度对三种小鼠模型的行为有显着影响。这些结果表明，AR 活动差异介导神经解剖学和行为，单独的 AR 活动不介导性别差异，并且神经发育过程与成年期 Q 束长度引起的体积变化的空间模式有关。他们还表明，成年期的雄激素敏感性不太可能导致自闭症相关行为或神经解剖学，尽管神经发育过程可能更早发挥作用。需要进一步研究性别差异、发育、其他行为和其他性别特异性机制，以更好地了解 AR 敏感性、神经发育障碍及其患病率的性别差异。