小鼠结核模型。体外和体内研究。

Boris V Nikonenko, Colleen Hanrahan
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引用次数: 0

摘要

模拟人类对结核病的整个易感性和耐药性的动物模型将有助于研究结核病的发病机制、宿主防御机制以及测试前瞻性的预防性和治疗性结核病疫苗和药物。近亲繁殖的小鼠菌株被广泛和成功地用于模拟人类结核病和研究宿主-分枝杆菌相互作用的机制。在这里,我们考虑了结核病小鼠模型的许多方面。我们分析了分枝杆菌感染途径和剂量对结核病病程的影响,并讨论了这些途径与人类自然感染途径的一致性。小鼠模型的优势在于可以获得数百种具有不同遗传背景的近交系。它允许对小鼠对结核病的易感性/抗性进行遗传分析。具有基因型、重组型、重组近交系、重组基因型、突变型等特定性状的小鼠品系,通过全基因组筛选,绘制出控制这些性状的位点。基因插入或靶向突变(基因敲除)的转基因小鼠品系是研究特定基因控制抗结核免疫作用的有效工具。具有细胞因子、趋化因子、细胞亚群、细胞受体和酶敲除基因的小鼠被广泛用于确定结核病控制机制。本文综述了一种用于抗结核疫苗和药物试验的小鼠模型。此外,我们还介绍了结核病免疫的一些重要现象——潜伏性结核/再激活和对结核病的免疫记忆。
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Murine Model of Tuberculosis. In vitro and in vivo Study.

Animal models that mimic the whole spectrum of susceptibility and resistance of human populations to tuberculosis would be useful for studying pathogenesis of tuberculosis, mechanisms of the host defense, and for testing prospective prophylactic and therapeutic tuberculosis vaccines and drugs. Inbred mouse strains are broadly and successfully used to model human tuberculosis and study mechanisms of host-mycobacteria interaction. Here we consider numerous aspects of murine models of tuberculosis. We analyze the course of tuberculosis depending on route and dosage of mycobacterial infection, and discuss the conformity of these approaches to the natural route of human infection. The advantage of the mouse model is provided by the availability of hundreds of inbred strains with different genetic background. It allows a genetic analysis of the mouse susceptibility/resistance to tuberculosis. Mouse strains with specific properties such as congenic, recombinant, recombinant inbred, recombinant congenic, mutant and usage of whole genome screening led to mapping loci controlling these traits. Transgenic mouse strains with gene insertion or targeted mutation (knock-out of a gene) are very effective tools for studying the role of specific genes controlling the anti-tuberculosis immunity. Mice with knock-out genes for cytokines, chemokines, cell subpopulations, cell receptors, and enzymes are broadly used to identify the mechanisms of tuberculosis control. In this review we examine a mouse model for anti-tuberculosis vaccine and drug testing. In addition, we present some important phenomena of tuberculosis immunity - latent tuberculosis/reactivation and immunological memory to tuberculosis.

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