Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, South Glamorgan, United Kingdom.
PLoS One. 2013 Aug 23;8(8):e73699. doi: 10.1371/journal.pone.0073699. eCollection 2013.
Whilst gonadal hormones can substantially influence sexual differentiation of the brain, recent findings have suggested that sex-linked genes may also directly influence neurodevelopment. Here we used the well-established murine 'four core genotype' (FCG) model on a gonadally-intact, outbred genetic background to characterise the contribution of Sry-dependent effects (i.e. those arising from the expression of the Y-linked Sry gene in the brain, or from hormonal sequelae of gonadal Sry expression) and direct effects of sex-linked genes other than Sry ('sex chromosome complement' effects) to sexually dimorphic mouse behavioural phenotypes. Over a 24 hour period, XX and XY gonadally female mice (lacking Sry) exhibited greater horizontal locomotor activity and reduced food consumption per unit bodyweight than XX and XY gonadally male mice (possessing Sry); in two behavioural tests (the elevated plus and zero mazes) XX and XY gonadally female mice showed evidence for increased anxiety-related behaviours relative to XX and XY gonadally male mice. Exploratory correlational analyses indicated that these Sry-dependent effects could not be simply explained by brain expression of the gene, nor by circulating testosterone levels. We also noted a sex chromosome complement effect on food (but not water) consumption whereby XY mice consumed more over a 24hr period than XX mice, and a sex chromosome complement effect in a third test of anxiety-related behaviour, the light-dark box. The present data suggest that: i) the male-specific factor Sry may influence activity and feeding behaviours in mice, and ii) dissociable feeding and anxiety-related murine phenotypes may be differentially modulated by Sry and by other sex-linked genes. Our results may have relevance for understanding the molecular underpinnings of sexually dimorphic behavioural phenotypes in healthy men and women, and in individuals with abnormal sex chromosome constitutions.
虽然性腺激素可以极大地影响大脑的性别分化，但最近的研究结果表明，性连锁基因也可能直接影响神经发育。在这里，我们使用了在性腺完整的、杂交遗传背景下成熟的鼠“四个核心基因型”（FCG）模型，来描述 Sry 依赖性效应（即源于大脑中 Y 连锁 Sry 基因的表达，或源于性腺 Sry 表达的激素后续影响）和除 Sry 之外的性连锁基因（“性染色体组成”效应）对雄性和雌性小鼠行为表型的直接影响。在 24 小时内，XX 和 XY 性腺雌性小鼠（缺乏 Sry）的水平运动活性高于 XX 和 XY 性腺雄性小鼠（具有 Sry），且单位体重的食物摄入量减少；在两项行为测试（高架十字迷宫和零迷宫）中，XX 和 XY 性腺雌性小鼠相对于 XX 和 XY 性腺雄性小鼠表现出焦虑相关行为增加的证据。探索性相关分析表明，这些 Sry 依赖性效应不能简单地用大脑中基因的表达或循环中的睾丸激素水平来解释。我们还注意到性染色体组成对食物（而非水）消耗的影响，即 XY 小鼠在 24 小时内消耗的食物多于 XX 小鼠，以及在第三个焦虑相关行为测试——明暗箱中观察到性染色体组成对焦虑相关行为的影响。本研究数据表明：i）雄性特异性因子 Sry 可能影响小鼠的活动和摄食行为，ii）可分离的摄食和焦虑相关的小鼠表型可能由 Sry 和其他性连锁基因以不同的方式调节。我们的研究结果可能有助于理解健康男性和女性以及具有异常性染色体组成的个体中，性别二态性行为表型的分子基础。
