A CRISPR/Cas9-engineered mouse carrying a conditional knockout allele for the early growth response-1 transcription factor

Abstract

Early growth response 1 (EGR1) mediates transcriptional programs that are indispensable for cell division, differentiation, and apoptosis in numerous physiologies and pathophysiologies. Whole-body EGR1 knockouts in mice (Egr1^KO ) have advanced our understanding of EGR1 function in an in vivo context. To extend the utility of the mouse to investigate EGR1 responses in a tissue- and/or cell-type-specific manner, we generated a mouse model in which exon 2 of the mouse Egr1 gene is floxed by CRISPR/Cas9 engineering. The floxed Egr1 alleles (Egr1^f/f ) are designed to enable spatiotemporal control of Cre-mediated EGR1 ablation in the mouse. To confirm that the Egr1^f/f alleles can be abrogated using a Cre driver, we crossed the Egr1^f/f mouse with a global Cre driver to generate the Egr1 conditional knockout (Egr1^d/d ) mouse in which EGR1 expression is ablated in all tissues. Genetic and protein analysis confirmed the absence of exon 2 and loss of EGR1 expression in the Egr1^d/d mouse, respectively. Moreover, the Egr1^d/d female exhibits overt reproductive phenotypes previously reported for the Egr1^KO mouse. Therefore, studies described in this short technical report underscore the potential utility of the murine Egr1 floxed allele to further resolve EGR1 function at a tissue- and/or cell-type-specific level.

Keywords: CRISPR/Cas9; early growth response-1; floxed; mouse; ovary; pituitary; uterus.