Humanized Mice for Infectious and Neurodegenerative disorders.

IF 2.7 3区 医学 Q3 VIROLOGY
Prasanta K Dash, Santhi Gorantla, Larisa Poluektova, Mahmudul Hasan, Emiko Waight, Chen Zhang, Milica Markovic, Benson Edagwa, Jatin Machhi, Katherine E Olson, Xinglong Wang, R Lee Mosley, Bhavesh Kevadiya, Howard E Gendelman
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Abstract

Humanized mice model human disease and as such are used commonly for research studies of infectious, degenerative and cancer disorders. Recent models also reflect hematopoiesis, natural immunity, neurobiology, and molecular pathways that influence disease pathobiology. A spectrum of immunodeficient mouse strains permit long-lived human progenitor cell engraftments. The presence of both innate and adaptive immunity enables high levels of human hematolymphoid reconstitution with cell susceptibility to a broad range of microbial infections. These mice also facilitate investigations of human pathobiology, natural disease processes and therapeutic efficacy in a broad spectrum of human disorders. However, a bridge between humans and mice requires a complete understanding of pathogen dose, co-morbidities, disease progression, environment, and genetics which can be mirrored in these mice. These must be considered for understanding of microbial susceptibility, prevention, and disease progression. With known common limitations for access to human tissues, evaluation of metabolic and physiological changes and limitations in large animal numbers, studies in mice prove important in planning human clinical trials. To these ends, this review serves to outline how humanized mice can be used in viral and pharmacologic research emphasizing both current and future studies of viral and neurodegenerative diseases. In all, humanized mouse provides cost-effective, high throughput studies of infection or degeneration in natural pathogen host cells, and the ability to test transmission and eradication of disease.

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用于感染性和神经退行性疾病的人源化小鼠。
人源化小鼠模拟人类疾病,因此通常用于传染病、退行性疾病和癌症疾病的研究。最近的模型还反映了造血、自然免疫、神经生物学和影响疾病病理生物学的分子途径。一系列免疫缺陷小鼠菌株允许植入长寿命的人类祖细胞。先天免疫和适应性免疫的存在使人类血液淋巴系统能够进行高水平的重建,细胞对广泛的微生物感染具有易感性。这些小鼠还促进了对人类病理生物学、自然疾病过程和广泛的人类疾病治疗效果的研究。然而,人类和小鼠之间的桥梁需要完全了解病原体剂量、合并症、疾病进展、环境和遗传学,这些都可以反映在这些小鼠身上。为了了解微生物易感性、预防和疾病进展,必须考虑这些因素。由于已知接触人体组织、评估代谢和生理变化以及大量动物的局限性的常见限制,对小鼠的研究在规划人类临床试验中被证明是重要的。为此,这篇综述概述了人源化小鼠如何用于病毒和药理学研究,强调了病毒和神经退行性疾病的当前和未来研究。总之,人源化小鼠提供了对自然病原体宿主细胞感染或变性的高成本效益、高通量研究,以及测试疾病传播和根除的能力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Retrovirology
Retrovirology 医学-病毒学
CiteScore
5.80
自引率
3.00%
发文量
24
审稿时长
>0 weeks
期刊介绍: Retrovirology is an open access, online journal that publishes stringently peer-reviewed, high-impact articles on host-pathogen interactions, fundamental mechanisms of replication, immune defenses, animal models, and clinical science relating to retroviruses. Retroviruses are pleiotropically found in animals. Well-described examples include avian, murine and primate retroviruses. Two human retroviruses are especially important pathogens. These are the human immunodeficiency virus, HIV, and the human T-cell leukemia virus, HTLV. HIV causes AIDS while HTLV-1 is the etiological agent for adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. Retrovirology aims to cover comprehensively all aspects of human and animal retrovirus research.
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