Interacting quantitative trait loci control phenotypic variation in murine estradiol-regulated responses.
Interacting quantitative trait loci control phenotypic variation in murine estradiol-regulated responses.
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DOI：
10.1210/endo.140.2.6521
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发表时间：
1999-02
期刊：
影响因子：
4.8
通讯作者：
Randall J. Roper;John S. Griffith;C. R. Lyttle;R. Doerge;Andrew McNabb;Robert E. Broadbent;Cory Teuscher
中科院分区：
文献类型：
--
作者：
Randall J. Roper;John S. Griffith;C. R. Lyttle;R. Doerge;Andrew McNabb;Robert E. Broadbent;Cory Teuscher
类固醇激素雌二醇（E2）在体内可引起全身和子宫反应。例如，E2治疗卵巢切除的成年和性未成熟啮齿动物导致子宫白细胞浸润，细胞增殖和器官生长。E2调节的生长也与多种正常和病理表型相关。历史上，子宫生长反应已被用作理解E2依赖性生长的分子和生化机制的关键模型。在这项研究中，基因组排阻作图确定了两个数量性状位点（QTL）的小鼠，EST 2和EST 3的5号和11号染色体上，分别控制子宫湿重的表型变异。这两个QTL都与多种E2调控基因相连，表明它们可能代表保守基因复合体中的位点，这些基因复合体在介导E2的作用中发挥重要作用。使用子宫白细胞反应和湿重的相互作用和多性状分析表明，EST 4，染色体10上的QTL，可能编码一个相互作用的因素，影响在这两个反应的数量变化。我们的研究结果表明，E2依赖的反应可以遗传控制，遗传基础可能是在许多E2依赖的表型观察到的变化。
The steroid hormone estradiol (E2) elicits a spectrum of systemic and uterotropic responses in vivo. For example, E2 treatment of ovariectomized adult and sexually immature rodents leads to uterine leukocytic infiltration, cell proliferation, and organ growth. E2-regulated growth is also associated with a variety of normal and pathological phenotypes. Historically, the uterine growth response has been used as the key model to understand the molecular and biochemical mechanisms underlying E2-dependent growth. In this study, genome exclusion mapping identified two quantitative trait loci (QTL) in the mouse, Est2 and Est3 on chromosomes 5 and 11, respectively, that control the phenotypic variation in uterine wet weight. Both QTL are linked to a variety of E2-regulated genes, suggesting that they may represent loci within conserved gene complexes that play fundamental roles in mediating the effects of E2. Interaction and multiple trait analyses using the uterine leukocyte response and wet weight suggest that Est4, a QTL on chromosome 10, may encode an interacting factor that influences the quantitative variation in both responses. Our results show that E2-dependent responses can be genetically controlled and that a genetic basis may underlie the variation observed in many E2-dependent phenotypes.