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HIV-1长末端重复序列激活模型:转基因小鼠皮肤中多种药物的评估

HIV-1 LTR activation model: evaluation of various agents in skin of transgenic mice.

作者信息

Morrey J D, Bourn S M, Bunch T D, Sidwell R W, Rosen C A

机构信息

Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan 84322-5600.

出版信息

J Acquir Immune Defic Syndr (1988). 1992 Dec;5(12):1195-203.

PMID:1453330
Abstract

Mice containing the HIV-1 long terminal repeat (LTR) regulating the expression of firefly luciferase reporter gene were investigated for their use as a model for activation of the LTR. As a limited test of this model, a number of different factors were screened for their ability to affect reporter gene activities in the skin. Reporter gene levels were increased in the skin by topical treatment of dimethylsulfoxide, retinoic acid, phorbol ester, ultraviolet light, and hydrogen peroxide, all of which have previously been shown to cause increased HIV production in cultured human cells. Topically applied arachidonic acid, histamine, ethanol, acetone, and methanol did not increase reporter gene activities. A lack of published reports on activation of HIV-1 in human cells by these agents suggests that they do not activate viral expression in human cells, which corroborates with the findings of this report. Minor forms of skin wounding and intraperitoneally administered psoralen plus ultraviolet light also increased reporter gene activities in skin. Control and test treatments could be performed on the same mouse and repetitive samples could be obtained from each treatment area. These transgenic mice might be useful as predictive models for regulation of the LTR in epidermal or dendritic cells.

摘要

对含有调控萤火虫荧光素酶报告基因表达的HIV-1长末端重复序列(LTR)的小鼠进行了研究,以评估其作为LTR激活模型的用途。作为对该模型的有限测试,筛选了多种不同因素影响皮肤中报告基因活性的能力。通过局部应用二甲亚砜、视黄酸、佛波酯、紫外线和过氧化氢,皮肤中的报告基因水平升高,所有这些物质先前已被证明可导致培养的人细胞中HIV产生增加。局部应用花生四烯酸、组胺、乙醇、丙酮和甲醇未增加报告基因活性。关于这些试剂在人细胞中激活HIV-1的已发表报告的缺乏表明它们不会激活人细胞中的病毒表达,这与本报告的发现一致。轻微形式的皮肤损伤以及腹腔注射补骨脂素加紫外线也增加了皮肤中报告基因的活性。对照和测试处理可在同一只小鼠上进行,并且可从每个处理区域获得重复样本。这些转基因小鼠可用作表皮或树突状细胞中LTR调控的预测模型。

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引用本文的文献

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Rapid in vivo functional analysis of transgenes in mice using whole body imaging of luciferase expression.利用荧光素酶表达的全身成像对小鼠体内转基因进行快速功能分析。
Transgenic Res. 2001 Oct;10(5):423-34. doi: 10.1023/a:1012042506002.
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Imaging brain structure and function, infection and gene expression in the body using light.利用光对大脑结构与功能、身体中的感染及基因表达进行成像。
Philos Trans R Soc Lond B Biol Sci. 1997 Jun 29;352(1354):755-61. doi: 10.1098/rstb.1997.0059.
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Reporter genes in transgenic mice.转基因小鼠中的报告基因。
Transgenic Res. 1994 May;3(3):182-94. doi: 10.1007/BF01973986.