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Morphologic and Immunohistochemical Characterization of Spontaneous Lymphoma/Leukemia in NSG Mice.
Veterinary Pathology ( IF 2.3 ) Pub Date : 2019-11-18 , DOI: 10.1177/0300985819882631
Heather Tillman 1 , Laura J Janke 1 , Amy Funk 2 , Peter Vogel 1 , Jerold E Rehg 1
Affiliation  

The NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ strain (NOD scid gamma, NSG) is a severely immunodeficient inbred laboratory mouse used for preclinical studies because it is amenable to engraftment with human cells. Combining scid and Il2rgnull mutations results in severe immunodeficiency by impairing the maturation, survival, and functionality of interleukin 2-dependent immune cells, including T, B, and natural killer lymphocytes. While NSG mice are reportedly resistant to developing spontaneous lymphomas/leukemias, there are reports of hematopoietic cancers developing. In this study, we characterized the immunophenotype of spontaneous lymphoma/leukemia in 12 NSG mice (20 to 38 weeks old). The mice had a combination of grossly enlarged thymus, spleen, or lymph nodes and variable histologic involvement of the bone marrow and other tissues. All 12 lymphomas were diffusely CD3, TDT, and CD4 positive, and 11 of 12 were also positive for CD8, which together was consistent with precursor T-cell lymphoblastic lymphoma/leukemia (pre-T-LBL). A subset of NSG tissues from all mice and neoplastic lymphocytes from 8 of 12 cases had strong immunoreactivity for retroviral p30 core protein, suggesting an association with a viral infection. These data highlight that NSG mice may develop T-cell lymphoma at low frequency, necessitating the recognition of this spontaneously arising disease when interpreting studies.

中文翻译:

NSG 小鼠自发性淋巴瘤/白血病的形态学和免疫组织化学特征。

NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ 品系(NOD scid gamma,NSG)是一种严重免疫缺陷的近交实验室小鼠,用于临床前研究,因为它适合植入人体细胞。结合 scid 和 Il2rgnull 突变会损害白介素 2 依赖性免疫细胞(包括 T、B 和自然杀伤淋巴细胞)的成熟、存活和功能,从而导致严重的免疫缺陷。虽然据报道 NSG 小鼠对发展自发性淋巴瘤/白血病具有抗性,但有报道称会发展成造血系统癌症。在这项研究中,我们对 12 只 NSG 小鼠(20 至 38 周龄)的自发性淋巴瘤/白血病的免疫表型进行了表征。这些小鼠的胸腺、脾脏或淋巴结明显增大,骨髓和其他组织的组织学受累程度不一。所有 12 例淋巴瘤均为弥漫性 CD3、TDT 和 CD4 阳性,12 例中有 11 例 CD8 也呈阳性,这与前体 T 细胞淋巴母细胞淋巴瘤/白血病 (pre-T-LBL) 一致。所有小鼠的一部分 NSG 组织和 12 例中有 8 例的肿瘤淋巴细胞对逆转录病毒 p30 核心蛋白具有很强的免疫反应性,表明与病毒感染有关。这些数据强调,NSG 小鼠可能会​​以低频率发展成 T 细胞淋巴瘤,因此在解释研究时需要识别这种自发性疾病。所有小鼠的一部分 NSG 组织和 12 例中有 8 例的肿瘤淋巴细胞对逆转录病毒 p30 核心蛋白具有很强的免疫反应性,表明与病毒感染有关。这些数据强调,NSG 小鼠可能会​​以低频率发展成 T 细胞淋巴瘤,因此在解释研究时需要识别这种自发性疾病。所有小鼠的一部分 NSG 组织和 12 例中有 8 例的肿瘤淋巴细胞对逆转录病毒 p30 核心蛋白具有很强的免疫反应性,表明与病毒感染有关。这些数据强调,NSG 小鼠可能会​​以低频率发展成 T 细胞淋巴瘤,因此在解释研究时需要识别这种自发性疾病。
更新日期:2019-11-01
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