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利用沙眼衣原体雌性生殖道感染小鼠模型鉴定候选基因。

Identification of candidate genes using the murine model of female genital tract infection with Chlamydia trachomatis.

作者信息

Lyons J M, Igietseme J U, Black C M, Morré S A

机构信息

Integrated Disease Modeling, Claremont, California 91711, USA.

出版信息

Drugs Today (Barc). 2009 Nov;45 Suppl B:51-9.

Abstract

The integrated approach to the study of female genital tract infection (GTI) with Chlamydia trachomatis is a conceptual framework through which a consistent and comprehensive evidence-based understanding of C. trachomatis GTI could evolve. One application of this approach has been to identify candidate genes that may play a role in the course and severity of C. trachomatis GTI in women, using human clinical and genetic data together with results obtained in the female mouse model to guide the selection process This model has been proven robust enough: i) to identify stable phenotypic differences in the course and outcome of GTI among commonly used immunocompetent inbred mouse stains that are used in the construction of gene knockout (KO) and transgenic mice; as well as ii) to serve as a platform in which to assess the influence of genetic differences among human genital tract isolates of C. trachomatis as well as between this biovar and the mouse biovar, Chlamydia muridarum. This review presents a summary of published and unpublished results from 25 years of studies in immunodeficient and gene-deficient KO mice that both inform our present understanding of the immunogenetics of C. trachomatis GTI and serve to guide candidate gene selection.

摘要

研究沙眼衣原体引起的女性生殖道感染(GTI)的综合方法是一个概念框架,通过该框架,可以逐步形成对沙眼衣原体GTI的连贯且全面的循证理解。该方法的一个应用是利用人类临床和遗传数据以及在雌性小鼠模型中获得的结果来指导筛选过程,从而确定可能在女性沙眼衣原体GTI的病程和严重程度中起作用的候选基因。该模型已被证明足够强大:其一,能够在用于构建基因敲除(KO)和转基因小鼠的常用免疫活性近交小鼠品系中,识别GTI病程和结果中的稳定表型差异;其二,可作为一个平台,用以评估沙眼衣原体人类生殖道分离株之间以及该生物变种与小鼠生物变种——鼠衣原体之间的遗传差异影响。本综述总结了在免疫缺陷和基因缺陷KO小鼠中进行的25年研究的已发表和未发表结果,这些结果既为我们目前对沙眼衣原体GTI免疫遗传学的理解提供了依据,也有助于指导候选基因的选择。

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