دورية أكاديمية
Genetic Study of Elf5 and Ehf in the Mouse Salivary Gland.
| العنوان: | Genetic Study of Elf5 and Ehf in the Mouse Salivary Gland. |
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| المؤلفون: | Song EAC; Department of Oral Biology, School of Dental Medicine, State University of New York at Buffalo, Buffalo, NY, USA., Smalley K; Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA., Oyelakin A; Department of Oral Biology, School of Dental Medicine, State University of New York at Buffalo, Buffalo, NY, USA., Horeth E; Department of Oral Biology, School of Dental Medicine, State University of New York at Buffalo, Buffalo, NY, USA., Che M; Department of Oral Biology, School of Dental Medicine, State University of New York at Buffalo, Buffalo, NY, USA., Wrynn T; Department of Oral Biology, School of Dental Medicine, State University of New York at Buffalo, Buffalo, NY, USA., Osinski J; Department of Oral Biology, School of Dental Medicine, State University of New York at Buffalo, Buffalo, NY, USA., Romano RA; Department of Oral Biology, School of Dental Medicine, State University of New York at Buffalo, Buffalo, NY, USA.; Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA., Sinha S; Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA. |
| المصدر: | Journal of dental research [J Dent Res] 2023 Mar; Vol. 102 (3), pp. 340-348. Date of Electronic Publication: 2022 Nov 08. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Sage Country of Publication: United States NLM ID: 0354343 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1544-0591 (Electronic) Linking ISSN: 00220345 NLM ISO Abbreviation: J Dent Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Thousand Oaks, CA : Sage Original Publication: Chicago, American Dental Assn. [etc.] |
| مواضيع طبية MeSH: | DNA-Binding Proteins*/genetics , DNA-Binding Proteins*/metabolism , Transcription Factors*/metabolism, Male ; Mice ; Animals ; Salivary Glands/metabolism |
| مستخلص: | Salivary gland (SG) development, maturation, and homeostasis require coordinated roles of transcription factors (TFs) that dictate specific cell identities and fate. The ETS family of proteins are important transcriptional drivers of diverse cell lineages, tissue development, and differentiation programs and hence are also likely to play an important role in the SG. Here we have leveraged genomic and epigenomic data of the SG to examine the expression profile of ETS genes and identified 2 closely related paralogs, Elf5 and Ehf, that are highly expressed in distinct epithelial subpopulations. By using a well-defined mouse knockout model of Elf5, we show that Elf5, despite its enriched expression in the acinar cells, is functionally dispensable for maintaining the homeostatic state of the adult SG epithelium. The lack of a discernible phenotype of the Elf5-null SG might be due to possible functional redundancy with Ehf or other ETS factors. To probe this possibility and to examine the specific consequences of Ehf loss in the SG, we used CRISPR-Cas9 to generate mice in which the DNA-binding ETS domain of Ehf is disrupted due to an insertion mutation. We demonstrate that the Ehf mutant (EhfMut) mice exhibit a distinct cellular phenotype with decreased granular convoluted tubules that are accompanied by an increased accumulation of the intercalated Sox9-positive ductal cell population. Interestingly, the ductal phenotype of the EhfMut animals is highly pronounced in males, reaffirming the established sexual dimorphism of the SG that exists in rodents. Our results show that unlike Elf5, Ehf plays a nonredundant role in directing ductal cell differentiation of the SG and highlights the phenotypic subtlety in mutant mice of closely related TFs and the importance of careful consideration of cell type-specific studies. |
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| معلومات مُعتمدة: | T32 DE023526 United States DE NIDCR NIH HHS |
| فهرسة مساهمة: | Keywords: ETS; cell fate; gene expression; salivary glands |
| المشرفين على المادة: | 0 (DNA-Binding Proteins) 0 (Transcription Factors) |
| تواريخ الأحداث: | Date Created: 20221109 Date Completed: 20230223 Latest Revision: 20240302 |
| رمز التحديث: | 20240302 |
| مُعرف محوري في PubMed: | PMC9947810 |
| DOI: | 10.1177/00220345221130258 |
| PMID: | 36348499 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1544-0591 |
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| DOI: | 10.1177/00220345221130258 |