A novel mouse model of adult T‐cell leukemia cell invasion into the spinal cord.
A novel mouse model of adult T‐cell leukemia cell invasion into the spinal cord.
复制标题
成人 T 细胞白血病细胞侵入脊髓的新型小鼠模型。
DOI：
10.1002/ame2.12053
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
K.
中科院分区：
文献类型：
--
作者：
Ohsugi;T.;Tanaka;S.;Iwasaki;K.;Nagano;Y.;Kozako;T.;Matsuda;K.;Hirose;T. and Takehana;K.
成人T细胞白血病（ATL）是由人类T细胞白血病病毒I型感染引起的成熟T细胞恶性肿瘤，10%～25%的患者表现出中枢神经系统（CNS）受累。中枢神经系统受累会显着降低生存率，并且中枢神经系统受累没有有效的治疗方法。因此，需要合适的动物模型来评估新药对累及中枢神经系统的ATL进展的抑制作用。在这里，我们使用在耳后区域肌肉注射 ATL 细胞的 NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ 小鼠建立了累及 CNS 的 ATL 小鼠模型，这些小鼠表现出截瘫。在 5 周龄时肌内 (I.M.) 接种 ATL 细胞的 10 只小鼠中，8 只 (80%) 表现出下肢轻瘫，而皮下 (S.C.) 接种 ATL 细胞的 10 只小鼠均未表现出下肢轻瘫。在肌注组中，PCR 在胸椎和腰椎中检测到 HTLV-1 特异性基因；然而，在 S.C. 组中，椎骨的 HTLV-1 基因呈阴性。组织学分析显示，肌注组小鼠的胸椎肿瘤发生率特别高，其特点是注射细胞的积累。骨髓中肿瘤细胞浸润相对较高。在脊髓胸椎中观察到肿瘤肿块侵犯软脑膜外引起的脊髓压迫。总之，我们报道了一种伴有截瘫的肿瘤生长小鼠模型，该模型可用于评估涉及中枢神经系统的 ATL 新型治疗药物。
Adult T‐cell leukemia (ATL) is a mature T‐cell malignancy caused by human T‐cell leukemia virus type I infection, and 10%‐25% of patients show central nervous system (CNS) involvement. CNS involvement significantly reduces survival and there are no effective treatments for CNS involvement. Therefore, an appropriate animal model is required to evaluate the inhibitory effects of novel drugs on the progression of ATL with CNS involvement. Here, we established a mouse model of ATL with CNS involvement using NOD.Cg‐PrkdcscidIl2rgtm1Wjl/SzJ mice inoculated with ATL cells intramuscularly in the postauricular region, and these mice showed paraparesis. Of the 10 mice inoculated with ATL cells intramuscularly (I.M.) at 5 weeks of age, 8 (80%) showed paraparesis, whereas none of the 10 mice inoculated with ATL cells subcutaneously (S.C.) showed paraparesis. In the I.M. group, PCR detected HTLV‐1‐specific genes in the thoracic and lumbar vertebrae; however, in the S.C. group, the vertebrae were negative for HTLV‐1 genes. Histological analysis revealed a particularly high incidence of tumors, characterized by accumulation of the injected cells, in the thoracic vertebrae of mice in the I.M. group. Tumor cell infiltration was relatively high in the bone marrow. Spinal cord compression caused by invasion of the tumor mass outside the pia mater was observed in the thoracic vertebrae of the spinal cord. In conclusion, we have reported a mouse model of tumor growth with paraparesis that may be used to assess novel therapeutic agents for ATL with CNS involvement.