Prkdc和Il2rg双敲除免疫缺陷小鼠的构建和初步应用
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E-mail: laiyana@njmu.edu.cn

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江苏省自然科学基金(BE2019730)。


Establishment and preliminary application of the immune ⁃ deficient mice models with Prkdc/Il2rg knockout
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    摘要:

    目的:构建NOD背景免疫缺陷小鼠,作为新的人源肿瘤异种移植(patient⁃derived xenograft,PDX)模型。方法:利用 CRISPR/Cas9技术获得NOD背景Prkdc和Il2rg双基因敲除小鼠,通过正常繁育得到能够稳定遗传的纯合子后代(命名为NYG 小鼠),流式细胞术检测小鼠外周血免疫细胞比例,移植接种新鲜肿瘤组织,观察记录肿瘤生长状况及HE染色观察传代PDX 肿瘤形态学特点。结果:NYG小鼠外周血小鼠无成熟的T细胞、B细胞和NK细胞表达,对移植的患者肿瘤组织几乎没有排斥反应,组织病理学表型及免疫系统未见明显异常。结论:成功构建NYG小鼠免疫缺陷小鼠,为肿瘤学基础理论及应用研究提供了新的PDX动物模型。

    Abstract:

    Objective:This srudy aims to establish a patient ⁃derived xenograft(PDX)model of NOD background immunodeficient mice for human cancer preclinical and biological research. Methods:NOD ⁃ PrkdcscidIl2rgnull mice were obtained by CRISPR/cas9 technology,and homozygous offspring with stable inheritance were obtained through normal breeding. The proportion of immune cells in peripheral blood of mice was monitored by flow cytometry. Fresh tumor tissues were transplanted and inoculated. The tumor growth status and the morphological characteristics of passaged PDX tumors were observed and recorded. Results:There was no expression of mature T,B and NK cells in peripheral blood of NYG mice. There was almost no rejection to human cells and tissues,and there was no obvious abnormality in histopathological phenotype and immune system. Conclusion:NYG mice and immunodeficient mice were successfully constructed,which provided a new PDX animal model for the basic theory and application of oncology.

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尹媛,曾文滔,周建丽,梅云,王颖,李建民,赖娅娜. Prkdc和Il2rg双敲除免疫缺陷小鼠的构建和初步应用[J].南京医科大学学报(自然科学版),2022,42(8):1107-1111

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  • 在线发布日期: 2022-08-07
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