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转基因小鼠中一个杂交基因的性二态性和生长激素调节

Sexual dimorphism and growth hormone regulation of a hybrid gene in transgenic mice.

作者信息

al-Shawi R, Wallace H, Harrison S, Jones C, Johnson D, Bishop J O

机构信息

Agricultural and Food Research Council Centre for Genome Research, University of Edinburgh, United Kingdom.

出版信息

Mol Endocrinol. 1992 Feb;6(2):181-90. doi: 10.1210/mend.6.2.1373818.

DOI:10.1210/mend.6.2.1373818
PMID:1373818
Abstract

The sexually dimorphic expression of the urinary protein genes of mice (Mup genes) in the liver is mediated by the different male and female temporal patterns of circulating GH. Normal females were induced to male levels when GH was administered by injection to mimic the male GH pattern, showing that expression at the male level does not require a male sex steroid status in addition to intermittent GH. Two Mup-alpha 2u-globulin hybrid transgenes with different Mup gene promoters showed sexually dimorphic expression, and their expression in females increased to male levels upon testosterone treatment. GH-deficient (lit/lit) mice did not express these transgenes, and GH-deficient females did not respond to testosterone treatment, showing that GH was required for induction. Both normal and GH-deficient females were induced to male levels when GH was administered by injection. This is the first report of a transgene responsive to GH. A transgene consisting of a Mup promoter fused to a Herpes simplex virus thymidine kinase reporter sequence also showed sexual dimorphism, although to a lesser degree. It was expressed at the same level in normal females and GH-deficient mice of both sexes and was induced when GH-deficient mice were treated with GH. We propose that this transgene has a basal constitutive expression, possibly due to the absence of any rodent DNA downstream of the promoter. Since expression of the transgene was significantly induced by GH, the GH response is due at least in part to sequences in the promoter region.

摘要

小鼠肝脏中尿蛋白基因(Mup基因)的性别二态性表达是由循环生长激素(GH)在雄性和雌性中的不同时间模式介导的。当通过注射给予生长激素以模拟雄性生长激素模式时,正常雌性被诱导到雄性水平,这表明除了间歇性生长激素外,雄性水平的表达不需要雄性性激素状态。两个具有不同Mup基因启动子的Mup-α2u球蛋白杂交转基因显示出性别二态性表达,并且它们在雌性中的表达在睾酮处理后增加到雄性水平。生长激素缺乏(lit/lit)小鼠不表达这些转基因,并且生长激素缺乏的雌性对睾酮处理没有反应,表明诱导需要生长激素。当通过注射给予生长激素时,正常和生长激素缺乏的雌性都被诱导到雄性水平。这是关于对生长激素有反应的转基因的首次报道。一个由Mup启动子与单纯疱疹病毒胸苷激酶报告序列融合而成的转基因也显示出性别二态性,尽管程度较小。它在正常雌性和两性生长激素缺乏小鼠中以相同水平表达,并且当生长激素缺乏小鼠用生长激素处理时被诱导。我们提出这个转基因具有基础组成型表达,可能是由于启动子下游没有任何啮齿动物DNA。由于转基因的表达被生长激素显著诱导,生长激素反应至少部分归因于启动子区域中的序列。

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