H-2b MHC等位基因稳定遗传后通过BALB/cBy UBC-GFP转基因消除4T1哺乳动物肿瘤细胞。

Candice A Grzelak, Cyrus M Ghajar
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引用次数: 0

摘要

人类泛素C启动子(UBC)驱动的GFP转基因小鼠(UBC-GFP)转基因整合位点最近被定位到17号染色体,与MHC基因座紧密相连。在这项研究中,我们证明了该插入位点在回交的UBC-GFP BALB/c同源菌株[CByJ.B6-Tg(UBC-GFP)30Scha/J]中的功能结果:对移植的“同源”4T1乳腺肿瘤细胞的排斥反应。BALB/c衍生的4T1细胞的排斥很可能是由于BALB/c UBC-GFP菌株对C57BL/6衍生的H-2b(而不是原型H-2d)的稳定遗传而导致的MHC失配的结果。这些数据对于之前使用UBC-GFP同源菌株进行同基因MHC匹配和异基因MHC不匹配研究的研究人员来说是一个宝贵的资源,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影响,以此提高科学严谨性和可重复性。
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Elimination of 4T1 Mammary Tumor Cells by BALB/cBy UBC-GFP Transgenics following Stable Inheritance of the H-2b MHC Allele.

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.

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