The Jackson Laboratory for Mouse Genetics, 600 Main Street, Bar Harbor, ME 04609, USA.
The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06032, USA.
Dis Model Mech. 2022 Sep 1;15(9). doi: 10.1242/dmm.049457. Epub 2022 Aug 29.
The lack of genetically diverse preclinical animal models in basic biology and efficacy testing has been cited as a potential cause of failure in clinical trials. We developed and characterized five diverse RAG1 null mouse strains as models that allow xenografts to grow. In these strains, we characterized the growth of breast cancer, leukemia and glioma cell lines. We found a wide range of growth characteristics that were far more dependent on strain than tumor type. For the breast cancer cell line, we characterized the spectrum of xenograft/tumor growth at structural, histological, cellular and molecular levels across each strain, and found that each strain captures unique structural components of the stroma. Furthermore, we showed that the increase in tumor-infiltrating myeloid CD45+ cells and the amount of circulating cytokine IL-6 and chemokine KC (also known as CXCL1) is associated with a higher tumor size in different strains. This resource is available to study established human xenografts, as well as difficult-to-xenograft tumors and growth of hematopoietic stems cells, and to decipher the role of myeloid cells in the development of spontaneous cancers.
缺乏具有遗传多样性的临床前动物模型，是基础生物学和疗效测试中潜在的失败原因。我们开发并鉴定了 5 种不同的 RAG1 基因敲除小鼠品系作为允许异种移植物生长的模型。在这些品系中，我们鉴定了乳腺癌、白血病和神经胶质瘤细胞系的生长情况。我们发现了广泛的生长特征，这些特征与肿瘤类型相比，更依赖于品系。对于乳腺癌细胞系，我们在每个品系中，从结构、组织学、细胞和分子水平上，对异种移植/肿瘤生长的范围进行了鉴定，发现每个品系都能捕获基质的独特结构成分。此外，我们还表明，肿瘤浸润性髓样细胞 CD45+细胞的增加以及循环细胞因子 IL-6 和趋化因子 KC（也称为 CXCL1）的含量与不同品系中更高的肿瘤大小有关。这个资源可用于研究已建立的人源异种移植瘤，以及难以进行异种移植的肿瘤和造血干细胞的生长，并解析髓样细胞在自发性癌症发展中的作用。
