Gfi1Cremice have early onset progressive hearing loss and induce recombination in numerous inner ear non-hair cells.
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 Gfi1Cremouse 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 Gfi1Cremice 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 Gfi1Cremouse neonatal inner ear, primarily in inner ear resident macrophages, which outnumber the hair cells. We further show that heterozygous Gfi1Cremice 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 Gfi1Creheterozygous mice cochleae compared with their wild-type littermate controls. Given the broad use of the Gfi1Cremice, both for gene deletion and reporter gene activation, these data are significant and necessary for proper planning and interpretation of experiments.
Department of Otorhinolaryngology Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Maggie
M
Matern
Department of Special Education and Communication Disorders, University of Nebraska Lincoln, Lincoln, Nebraska 68583-0738, USA.
Sarath
S
Vijayakumar
Department of Otorhinolaryngology Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Zachary
Z
Margulies
Department of Otorhinolaryngology Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Beatrice
B
Milon
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Yang
Y
Song
Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Ran
R
Elkon
Department of Otorhinolaryngology Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Xiaoyu
X
Zhang
Department of Special Education and Communication Disorders, University of Nebraska Lincoln, Lincoln, Nebraska 68583-0738, USA.
Sherri M
SM
Jones
Department of Otorhinolaryngology Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.|Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA.|Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Ronna
R
Hertzano
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D007758:Ear, Inner / Q000473:pathology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D034381:Hearing Loss / Q000235:genetics* / Q000473:pathology*; D019426:Integrases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D011995:Recombination, Genetic; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; C079873:Gfi1 protein, mouse; D014157:Transcription Factors; C045073:Cre recombinase; D019426:Integrases