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Tissue-specific and hormonally regulated expression of a rat alpha 2u globulin gene in transgenic mice.

机译:转基因小鼠大鼠2U球蛋白基因的组织特异性和激素调节表达。

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To investigate the tissue-specific and hormonal regulation of the rat alpha 2u globulin gene family, we introduced one cloned member of the gene family into the mouse germ line and studied its expression in the resulting transgenic mice. Alpha 2u globulingene 207 was microinjected on a 7-kilobase DNA fragment, and four transgenic lines were analyzed. The transgene was expressed at very high levels, specifically in the liver and the preputial gland of adult male mice. The expression in male liver was first detected at puberty, and no expression was detected in female transgenic mice. This pattern of expression is similar to the expression of endogenous alpha 2u globulin genes in the rat but differs from the expression of the homologous mouse major urinary protein (MUP) gene family in that MUPs are synthesized in female liver and not in the male preputial gland. We conclude that these differences between rat alpha 2u globulin and mouse MUP gene expression are due to evolutionary differences in cis-acting regulatory elements. The expression of the alpha 2u globulin transgene in the liver was abolished by castration and fully restored after testosterone replacement. The expression could also be induced in the livers of female mice by treatment with either testosterone or dexamethasone, following ovariectomy and adrenalectomy. Therefore, the cis-acting elements responsible for regulation by these two hormones, as well as those responsible for tissue-specific expression, are closely linked to the alpha 2u globulin gene.
机译:为了研究大鼠2U球蛋白基因家族的组织特异性和激素调节,我们将基因家族的一个克隆成员引入小鼠胚芽线中,并在所得的转基因小鼠中研究了表达。 α2U球状烯207在7千碱基DNA片段上进行微调,分析了四种转基因系。转基因在非常高的水平上表达,特别是在肝脏和成年雄性小鼠的Proputial腺体中表达。在青春期首次检测雄性肝脏的表达,在雌性转基因小鼠中没有检测表达。这种表达模式类似于大鼠内源性α2u球蛋白基因的表达,但与同源小鼠主要泌尿蛋白(MUP)基因家族的表达不同,在该MUP中,在雌性肝脏中合成,而不是在雄性预腺中合成。我们得出结论,大鼠α2U球蛋白和小鼠MUP基因表达之间的这些差异是由于顺式作用调节元件的进化差异。通过阉割废除肝脏中α2u球蛋白转基因的表达,并在睾酮替代后完全恢复。在卵巢切除术和肾上腺切除术后,还可以通过用睾酮或地塞米松治疗在雌性小鼠的肝脏中诱导表达。因此,负责这两个激素调节的顺式作用元件以及负责组织特异性表达的那些与α2u球蛋白基因密切相关。

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