Phenotypic Diversity Caused by Differential Expression of SFTPC-Cre–Transgenic Alleles
| العنوان: | Phenotypic Diversity Caused by Differential Expression of SFTPC-Cre–Transgenic Alleles |
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| المؤلفون: | Jonathan K. Alder, Mark G. Roth, Mao Jiang, Daniel I Sullivan, Pattra Chun-On |
| المصدر: | Am J Respir Cell Mol Biol |
| بيانات النشر: | American Thoracic Society, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Pulmonary and Respiratory Medicine, Genetically modified mouse, Transgene, Clinical Biochemistry, Cre recombinase, Mice, Transgenic, Biology, Germline, Mice, 03 medical and health sciences, 0302 clinical medicine, Genes, Reporter, Testis, Animals, Humans, Cell Lineage, Telomeric Repeat Binding Protein 2, RNA, Messenger, Transgenes, Allele, Promoter Regions, Genetic, Spermatogenesis, Paternal Inheritance, Lung, Molecular Biology, Alleles, Cellular Senescence, Genetic Association Studies, Genetics, Integrases, Gene Expression Regulation, Developmental, Telomere Homeostasis, Cell Biology, Pulmonary Surfactant-Associated Protein C, Phenotype, Embryonic stem cell, Recombinant Proteins, Mice, Inbred C57BL, Major Technical Advances, 030104 developmental biology, 030228 respiratory system, Alveolar Epithelial Cells, Female, Genes, Lethal, Single-Cell Analysis |
| الوصف: | Type II alveolar epithelial cells (AEC2s) play an essential role in the function and maintenance of the pulmonary epithelium. Several transgenic mice have been developed to study the function of these cells in vivo by using the human SFTPC promoter to drive expression of Cre recombinase. The precise activity of each of these transgenic alleles has not been studied, and previous reports suggest that their activity can depend on breeding strategies. We bred mice with a conditional allele of the essential telomere capping protein TRF2 with two different SFTPC-Cre–transgenic strains and observed opposite phenotypes (100% lethality vs. 100% viability). We characterized the Cre recombinase activity in these two transgenic lines and found that the contrasting phenotypes were driven by difference in embryonic expression of the two transgenes, likely due to position effects or differences in the transgenic constructs. We also tested if SFTPC-Cre activity was dependent on maternal or paternal inheritance. When paternally inherited, both SFTPC-Cre alleles produced offspring with constitutive reporter activity independent of the inheritance of the Cre allele, suggesting that Cre recombinase was expressed in the male germline before meiosis. Immunohistochemical analysis of the testis showed reporter activity during spermatogenesis. Analysis of single-cell RNA sequencing data from murine and human testis demonstrated SFTPC expression uniquely during human spermatogenesis, suggesting that use of the human promoter in these constructs is responsible for male germline activity. Our data highlight the importance of careful analysis of transgenic allele activity and identify an SFTPC-Cre allele that is useful for panepithelial targeting in the mouse. |
| تدمد: | 1535-4989 1044-1549 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5105e57271f895cae3f617f236c5f32fTest https://doi.org/10.1165/rcmb.2019-0416maTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5105e57271f895cae3f617f236c5f32f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15354989 10441549 |
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