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用于 HTLV-1 感染和成人 T 细胞白血病的小鼠模型。

Mouse Models for HTLV-1 Infection and Adult T Cell Leukemia.

机构信息

Department of Microbiology, Faculty of Medicine, Kansai Medical University, Hirakata 573-1010, Osaka, Japan.

出版信息

Int J Mol Sci. 2023 Jul 21;24(14):11737. doi: 10.3390/ijms241411737.

Abstract

Adult T cell leukemia (ATL) is an aggressive hematologic disease caused by human T cell leukemia virus type 1 (HTLV-1) infection. Various animal models of HTLV-1 infection/ATL have been established to elucidate the pathogenesis of ATL and develop appropriate treatments. For analyses employing murine models, transgenic and immunodeficient mice are used because of the low infectivity of HTLV-1 in mice. Each mouse model has different characteristics that must be considered before use for different HTLV-1 research purposes. HTLV-1 and transgenic mice spontaneously develop tumors, and the roles of both Tax and HBZ in cell transformation and tumor growth have been established. Severely immunodeficient mice were able to be engrafted with ATL cell lines and have been used in preclinical studies of candidate molecules for the treatment of ATL. HTLV-1-infected humanized mice with an established human immune system are a suitable model to characterize cells in the early stages of HTLV-1 infection. This review outlines the characteristics of mouse models of HTLV-1 infection/ATL and describes progress made in elucidating the pathogenesis of ATL and developing related therapies using these mice.

摘要

成人 T 细胞白血病(ATL)是一种由人类 T 细胞白血病病毒 1(HTLV-1)感染引起的侵袭性血液系统疾病。为了阐明 ATL 的发病机制并开发出合适的治疗方法,已经建立了多种 HTLV-1 感染/ATL 的动物模型。由于 HTLV-1 在小鼠中的感染性较低,因此使用转基因和免疫缺陷小鼠进行采用鼠模型的分析。每种小鼠模型都有不同的特点,在用于不同的 HTLV-1 研究目的之前,必须考虑这些特点。HTLV-1 和转基因小鼠会自发地形成肿瘤,并且 Tax 和 HBZ 在细胞转化和肿瘤生长中的作用已经得到了确立。严重免疫缺陷的小鼠可以被 ATL 细胞系移植,并已用于 ATL 治疗候选分子的临床前研究。具有已建立的人类免疫系统的 HTLV-1 感染人源化小鼠是一种合适的模型,可用于描述 HTLV-1 感染早期阶段的细胞。本文概述了 HTLV-1 感染/ATL 小鼠模型的特点,并描述了使用这些小鼠阐明 ATL 发病机制和开发相关治疗方法方面的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c3c/10380921/2ef489102860/ijms-24-11737-g001.jpg

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