Here, we report inducible mosaic animal for perturbation (iMAP), a transgenic platform enabling in situ CRISPR targeting of at least 100 genes in parallel throughout the mouse body. iMAP combines Cre-loxP and CRISPR-Cas9 technologies and utilizes a germline-transmitted transgene carrying a large array of individually floxed, tandemly linked gRNA-coding units. Cre-mediated recombination triggers expression of all the gRNAs in the array but only one of them per cell, converting the mice to mosaic organisms suitable for phenotypic characterization and also for high-throughput derivation of conventional single-gene perturbation lines via breeding. Using gRNA representation as a readout, we mapped a miniature Perturb-Atlas cataloging the perturbations of 90 genes across 39 tissues, which yields rich insights into context-dependent gene functions and provides a glimpse of the potential of iMAP in genome decoding.

在这里，我们报告了用于扰动的诱导性嵌合动物（iMAP），这是一个转基因平台，能够在整个小鼠体内平行地原位CRISPR 靶向至少 100 个基因。iMAP 结合了 Cre-loxP 和 CRISPR-Cas9 技术，并利用种系传播的转基因，该转基因携带大量单独排列、串联连接的 gRNA 编码单元。Cre介导的重组触发阵列中所有gRNA的表达，但每个细胞仅表达一种，将小鼠转化为适合表型表征的嵌合生物，也适合通过育种高通量衍生传统单基因扰动系。使用 gRNA 表示作为读数，我们绘制了一个微型扰动图集，对 39 个组织中 90 个基因的扰动进行了编目，这对上下文相关的基因功能产生了丰富的见解，并让我们一睹 iMAP 在基因组解码方面的潜力。