Public Health Sciences Division/Translational Research Program, Fred Hutchinson Cancer Center, Seattle, WA; and.
Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA.
Immunohorizons. 2023 Jan 1;7(1):64-70. doi: 10.4049/immunohorizons.2200101.
The human ubiquitin C promoter (UBC)-driven GFP-transgenic mouse (UBC-GFP) transgene integration site was mapped recently to chromosome 17, linked closely to the MHC locus. In this study, we demonstrate a functional consequence of this insertion site in the backcrossed UBC-GFP BALB/c congenic strain [CByJ.B6-Tg(UBC-GFP) 30Scha/J]: rejection of transplanted "syngeneic" 4T1 mammary tumor cells. Rejection of BALB/c-derived 4T1 cells is in all likelihood a consequence of MHC mismatch due to stable inheritance of C57BL/6-derived H-2b (rather than prototypical H-2d) by the BALB/c UBC-GFP strain. These data are a valuable resource to researchers who have previously employed the UBC-GFP congenic strain for attempted syngeneic MHC-matched and allogenic MHC-mismatched studies, as their data likely require reinterpretation. Further, this study reemphasizes the impact of mapping transgene integration sites of commonly used mouse strains as a way of increasing scientific rigor and reproducibility.
最近,人类泛素 C 启动子 (UBC)-驱动 GFP 转基因小鼠 (UBC-GFP) 的转基因整合位点被定位到染色体 17 上,与 MHC 基因座紧密连锁。在这项研究中,我们证明了回交 UBC-GFP BALB/c 近交系 [CByJ.B6-Tg(UBC-GFP) 30Scha/J] 中该插入位点的一个功能后果:排斥移植的“同基因”4T1 乳腺肿瘤细胞。BALB/c 来源的 4T1 细胞的排斥很可能是由于 MHC 不匹配的结果,因为 BALB/c UBC-GFP 品系稳定地继承了 C57BL/6 来源的 H-2b(而不是典型的 H-2d)。对于之前曾使用 UBC-GFP 近交系进行同基因 MHC 匹配和同种异体 MHC 不匹配研究的研究人员来说,这些数据是有价值的资源,因为他们的数据可能需要重新解释。此外,这项研究再次强调了绘制常用小鼠品系的转基因整合位点的重要性,这是提高科学严谨性和可重复性的一种方式。