a non-specific effect associated with conditional transgene expression based on cre-loxp strategy in mice非特异性效应与条件相关转基因表达基于cre-loxp策略在老鼠身上.pdfVIP

A Non-Specific Effect Associated with Conditional Transgene Expression Based on Cre-loxP Strategy in Mice 1 ´ 2 1,2,3 Linghua Qiu , Jaime A. Rivera-Perez , Zuoshang Xu * 1 Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America, 2 Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America, 3 Neuroscience Program, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America Abstract Transgenes flanked by loxP sites have been widely used to generate transgenic mice where the transgene expression can be controlled spatially and temporally by Cre recombinase. Data from this approach has led to important conclusions in cancer, neurodevelopment and neurodegeneration. Using this approach to conditionally express micro RNAs (miRNAs) in mice, we found that Cre-mediated recombination in neural progenitor cells caused microcephaly in five of our ten independent transgenic lines. This effect was not associated with the types or the quantity of miRNAs being expressed, nor was it associated with specific target knockdown. Rather, it was correlated with the presence of multiple tandem transgene copies and inverted (head-to-head or tail-to-tail) transgene repeats. The presence of these inverted repeats caused a high level of cell death in the ventricular zone of the embryonic brain, where Cre was expressed. Therefore, results from this Cre- loxP approach to generate inducible transgenic alleles must be interpreted with caution and conclusions drawn in previous reports may need reexamination. ´ Citation: Qiu L, Rivera-Perez JA