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首页> 外文期刊>Genes, brain, and behavior >Sexual differentiation in the developing mouse brain: contributions of sex chromosome genes.
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Sexual differentiation in the developing mouse brain: contributions of sex chromosome genes.

机译:发育中的小鼠大脑中的性别分化:性染色体基因的贡献。

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摘要

Neural sexual differentiation begins during embryogenesis and continues after birth for a variable amount of time depending on the species and brain region. Because gonadal hormones were the first factors identified in neural sexual differentiation, their role in this process has eclipsed investigation of other factors. Here, we use a mouse with a spontaneous translocation that produces four different unique sets of sex chromosomes. Each genotype has one normal X-chromosome and a unique second sex chromosome creating the following genotypes: XY(*x) , XX, XY(*) , XX(Y) (*) . This Y(*) mouse line is used by several laboratories to study two human aneuploid conditions: Turner and Klinefelter syndromes. As sex chromosome number affects behavior and brain morphology, we surveyed brain gene expression at embryonic days 11.5 and 18.5 to isolate X-chromosome dose effects in the developing brain as possible mechanistic changes underlying the phenotypes. We compared gene expression differences between gonadal males and females as well as individuals with one vs. two X-chromosomes. We present data showing, in addition to genes reported to escape X-inactivation, a number of autosomal genes are differentially expressed between the sexes and in mice with different numbers of X-chromosomes. Based on our results, we can now identify the genes present in the region around the chromosomal break point that produces the Y(*) model. Our results also indicate an interaction between gonadal development and sex chromosome number that could further elucidate the role of sex chromosome genes and hormones in the sexual differentiation of behavior.
机译:神经性分化在胚胎发生期间开始,并在出生后持续一段时间,具体时间取决于物种和大脑区域。由于性腺激素是神经性分化中首先发现的因素,因此其在这一过程中的作用已使其他因素的研究黯然失色。在这里,我们使用具有自发易位的小鼠,该小鼠产生四组独特的性染色体。每个基因型都有一个正常的X染色体和一个唯一的第二性染色体,产生以下基因型:XY(* x),XX,XY(*),XX(Y)(*)。几个实验室使用了这种Y(*)小鼠品系来研究两种人类非整倍体疾病:特纳和克林费尔特综合征。由于性染色体数目影响行为和大脑形态,因此我们在胚胎第11.5和18.5天调查了大脑基因表达,以分离X染色体剂量对发育中的大脑的作用,以作为潜在的表型机制改变。我们比较了性腺雄性和雌性以及具有一个X染色体和两个X染色体的个体之间的基因表达差异。我们提供的数据显示,除报道逃避X灭活的基因外,许多常染色体基因在性别之间以及在具有不同X染色体数目的小鼠中差异表达。根据我们的结果,我们现在可以鉴定出产生Y(*)模型的染色体断裂点附近区域中的基因。我们的研究结果还表明,性腺发育与性染色体数目之间的相互作用可以进一步阐明性染色体基因和激素在行为的性别分化中的作用。

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