A CRISPR/Cas9-Engineered Mouse Carrying a Conditional Knockout Allele for the Early Growth Response-1 Transcription Factor

Authors

Vineet K Maurya
Yan Ying
Denise G Lanza
Jason D Heaney
John P Lydon

Publication Date

7-1-2023

Journal

Genesis

DOI

10.1002/dvg.23515

PMID

36949241

PMCID

PMC10514223

PubMedCentral® Posted Date

7-1-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Mice, Female, Animals, Transcription Factors, Alleles, CRISPR-Cas Systems, Exons, Mouse, early growth response-1, CRISPR/Cas9, floxed, pituitary, ovary, uterus

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 (Egr1KO) 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 (Egr1f/f) are designed to enable spatiotemporal control of Cre-mediated EGR1 ablation in the mouse. To confirm that the Egr1f/f alleles can be abrogated using a Cre driver, we crossed the Egr1f/f mouse with a global Cre driver to generate the Egr1 conditional knockout (Egr1d/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 Egr1d/d mouse respectively. Moreover, the Egr1d/d female exhibits overt reproductive phenotypes previously reported for the Egr1KO 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.

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