Gfi1^Cre mice have early onset progressive hearing loss and induce recombination in numerous inner ear non-hair cells

Authors

Maggie Matern, University of Maryland School of Medicine
Sarath Vijayakumar, University of Nebraska - LincolnFollow
Zachary Margulies, University of Maryland School of Medicine
Beatrice Milon, University of Maryland School of Medicine
Yang Song, University of Maryland School of Medicine
Ran Elkon, Sackler School of Medicine
Xiaoyu Zhang, University of Maryland School of Medicine
Sherri M. Jones, University of Nebraska-LincolnFollow
Ronna Hertzano, University of Maryland School of MedicineFollow

Document Type

Article

Date of this Version

2017

Citation

Matern, M. et al. Gfi1^Cre mice have early onset progressive hearing loss and induce recombination in numerous inner ear non-hair cells. Sci. Rep. 7, 42079; doi: 10.1038/srep42079 (2017).

Comments

This work is licensed under a Creative Commons Attribution 4.0 International License. Used by permission.

Abstract

Studies of developmental and functional biology largely rely on conditional expression of genes in a cell type-specific manner. Therefore, the importance of specificity and lack of inherent phenotypes for Cre-driver animals cannot be overemphasized. The Gfi1^Cre mouse is commonly used for conditional hair cell-specific gene deletion/reporter gene activation in the inner ear. Here, using immunofluorescence and flow cytometry, we show that the Gfi1^Cre mice produce a pattern of recombination that is not strictly limited to hair cells within the inner ear. We observe a broad expression of Cre recombinase in the Gfi1^Cre mouse neonatal inner ear, primarily in inner ear resident macrophages, which outnumber the hair cells. We further show that heterozygous Gfi1^Cre mice exhibit an early onset progressive hearing loss as compared with their wild-type littermates. Importantly, vestibular function remains intact in heterozygotes up to 10 months, the latest time point tested. Finally, we detect minor, but statistically significant, changes in expression of hair cell-enriched transcripts in the Gfi1^Cre heterozygous mice cochleae compared with their wild-type littermate controls. Given the broad use of the Gfi1^Cre mice, both for gene deletion and reporter gene activation, these data are significant and necessary for proper planning and interpretation of experiments.