First Author | Laster DJ | Year | 2023 |
Journal | iScience | Volume | 26 |
Issue | 8 | Pages | 107428 |
PubMed ID | 37575184 | Mgi Jnum | J:339330 |
Mgi Id | MGI:7519863 | Doi | 10.1016/j.isci.2023.107428 |
Citation | Laster DJ, et al. (2023) CRISPR interference provides increased cell type-specificity compared to the Cre-loxP system. iScience 26(8):107428 |
abstractText | Cre-mediated recombination is frequently used for cell type-specific loss of function (LOF) studies. A major limitation of this system is recombination in unwanted cell types. CRISPR interference (CRISPRi) has been used effectively for global LOF in mice. However, cell type-specific CRISPRi, independent of recombination-based systems, has not been reported. To test the feasibility of cell type-specific CRISPRi, we produced two novel knock-in mouse models that achieve gene suppression when used together: one expressing dCas9::KRAB under the control of a cell type-specific promoter and the other expressing a single guide RNA from a safe harbor locus. We then compared the phenotypes of mice in which the same gene was targeted by either CRISPRi or the Cre-loxP system, with cell specificity conferred by Dmp1 regulatory elements in both cases. We demonstrate that CRISPRi is effective for cell type-specific LOF and that it provides improved cell type-specificity compared to the Cre-loxP system. |