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Sex differences in the cardiac proteome in myocardial hypertrophy

心肌肥大中心脏蛋白质组的性别差异

基本信息

批准号：
79541460
负责人：
Professor Dr. Joachim Klose
金额：
--
依托单位：
Institut für Medizinische Genetik und Humangenetik (CVK)
依托单位国家：
德国
项目类别：
Research Units
财政年份：
2008
资助国家：
德国
起止时间：
2007-12-31 至 2014-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/79541460?language=en
关键词：
Sex differences cardiac proteome myocardial

项目摘要

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.

雄性和雌性哺乳动物基因组仅因性别特异性染色体上的少数基因存在差异，这一发现意味着绝大多数性二态性特征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，但受影响的基因数量却很大。如今，应用开发的技术来分析整个组织蛋白质组的蛋白质，可以系统地评估性别偏向的蛋白质表达，并阐明性别二态性在疾病发展和表达中的作用。我们将使用蛋白质组分析来研究男性和女性的心肌肥大 (MH)。我们的假设是，由于蛋白质-蛋白质相互作用的高度复杂网络，由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不同，并以这种方式影响蛋白质组中的性别二态性。这导致男性和女性之间以及个体之间的 MH 表型不同。我们将使用小鼠染色体替代品系作为动物模型来研究性别特异性蛋白多态性对 MH 发生的影响。