Bakiri Latifa, Tichet Mélanie, Marques Carolina, Thomsen Martin K, Allen Elizabeth A, Stolzlechner Stefanie, Cheng Ke, Matsuoka Kazuhiko, Squatrito Massimo, Hanahan Douglas, Wagner Erwin F
Laboratory Genes and Disease, Department of Laboratory Medicine, Medical University of Vienna, Vienna (MUW), Spitalgasse 23, 1090 Vienna, Austria.
Ludwig Institute for Cancer Research, Lausanne Branch; Swiss Institute for Experimental Cancer Research (ISREC), EPFL; Swiss Cancer Center Leman (SCCL); Agora Translational Cancer Research Center, Rue du Bugnon 25A, 1005 Lausanne, Switzerland.
Dis Model Mech. 2025 Jan 1;18(1). doi: 10.1242/dmm.052130. Epub 2025 Jan 31.
Genetically engineered mouse models (GEMMs) are instrumental for modelling local and systemic features of complex diseases, such as cancer. Non-invasive, longitudinal cell detection and monitoring in tumors, metastases and/or the micro-environment is paramount to achieve a better spatiotemporal understanding of cancer progression and to evaluate therapies in preclinical studies. Bioluminescent and fluorescent reporters marking tumor cells or their microenvironment are valuable for non-invasive cell detection and monitoring in vivo. Here, we report the generation of a dual reporter allele allowing simultaneous bioluminescence and fluorescence detection of cells that have undergone Cre-Lox recombination in mice. The single copy knock-in allele in the permissive collagen I locus was evaluated in the context of several cancer GEMMs, where Cre expression was achieved genetically or by ectopic virus-mediated delivery. The new reporter allele was also combined with gene-targeted alleles widely used in bone, prostate, brain and pancreas cancer research, as well as with alleles inserted into the commonly used Rosa26 and collagen I loci. This allele is, therefore, a useful addition to the portfolio of reporters to help advance preclinical research.
基因工程小鼠模型(GEMMs)有助于模拟复杂疾病(如癌症)的局部和全身特征。在肿瘤、转移灶和/或微环境中进行非侵入性的纵向细胞检测和监测,对于更好地从时空角度理解癌症进展以及在临床前研究中评估治疗方法至关重要。标记肿瘤细胞或其微环境的生物发光和荧光报告基因对于体内非侵入性细胞检测和监测很有价值。在此,我们报告了一种双报告基因等位基因的产生,该等位基因允许对小鼠中经历了Cre-Lox重组的细胞同时进行生物发光和荧光检测。在几个癌症GEMM背景下评估了在允许的胶原蛋白I基因座中的单拷贝敲入等位基因,其中Cre表达通过基因方式或异位病毒介导的递送实现。新的报告基因等位基因还与在骨癌、前列腺癌、脑癌和胰腺癌研究中广泛使用的基因靶向等位基因相结合,以及与插入常用的Rosa26和胶原蛋白I基因座的等位基因相结合。因此,该等位基因是报告基因组合中的一个有用补充,有助于推进临床前研究。