Sex differences in the cardiac proteome in myocardial hypertrophy

这一发现表明，雄性和雌性哺乳动物的基因组只有少数位于性别特异性染色体上的基因不同，这意味着绝大多数两性二态性状是由两性中存在的基因的差异表达和翻译造成的。尽管大多数差异的大小不大，但受影响基因的数量却是相当可观的。今天，用于分析组织蛋白质组范围内蛋白质的技术的应用，使系统地评估性别偏向的蛋白质表达和阐明性别二态性在疾病的发展和表达中的作用成为可能。我们将使用蛋白质组学分析来研究男性和女性的心肌肥厚（MH）。我们的假设是，由于高度复杂的蛋白质相互作用网络，性激素启动的蛋白质表达调节在男性和女性蛋白质组范围内是不同的。因此，基因和蛋白质的多态性在男性和女性中的作用是不同的，并且在一定程度上以这种方式在蛋白质组中的性别二态性。这导致雄性和雌性之间，甚至个体之间MH的表型不同。我们将使用小鼠染色体替代菌株作为动物模型，研究性别特异性蛋白多态性在MH发育中的影响。

The finding that male and female mammalian genomes differ by only a few genes located on sex-specific chromosomes implies that the vast majority of sexually dimorphic traits result from the differential expression and translation of genes that are present in both sexes. Although most differences are modest in size, the number of affected genes is substantial. Today the application of techniques developed to analyze the proteins of a tissue proteomewide enables the systematic evaluation of sex biased protein expression and the elucidation of the role of the sex-dimorphism in the development and expression of a disease. We will use proteome analysis to investigate myocardial hypertrophy (MH) in males and females. Our hypothesis is that due to highly complex networks of protein-protein interaction regulation of protein expression initiated by sex-hormones differs in males and females proteome-wide. As a consequence, polymorphisms in genes and proteins act in males and females differently and extent in this way sex-dimorphisms in the proteome. This leads to different phenotypes of MH between males and females, and, moreover between individuals. We will use chromosome substitution strains of the mouse as an animal model for studying the influence of sex-specific protein polymorphisms in the development of MH.