RNA-sequence analysis of mammary epithelial cells with and without DNp63 using tamoxifen driven conditional deletion of DNp63
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE137062 | GEO | 2022/09/05
REPOSITORIES: GEO
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Project description:RNA-sequence analysis of mammary epithelial cells with and without DNp63 using tamoxifen driven conditional deletion of DNp63
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Project description:CRE-loxP-mediated inactivation and activation of genes in mouse mammary epithelium have been widely used to study genetic pathways in normal development and neoplastic transformation in vivo. In 1997, we generated three distinct mouse lines carrying an identical MMTV-Cre transgene (lines A, D, and F). Because the presence of CRE recombinase can adversely affect the physiology of nonmammary cells, we explored whether transgenic females display lactational defects. Whereas dams from line D nurse their pups and display overtly normal mammary development, line A shows some impairment during lactation and females from line F completely fail to nurse their litters. The ability to nurse a litter correlates with the extent of alveolar development and differentiation. This study demonstrates the importance of including appropriate "Cre-only" controls and provides guidelines to avoid problems in data interpretation.
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Project description:To investigate the role of Egfr in the cerebreal cortex and hippocampal formation we conditionally deleted it using a floxed allele in combination with the Nestin-cre transgene. Cortices at P5 post-natal stage were harvested and split into rostral and caudal halves and RNA extracted and sequenced
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Project description:Atypical PKCiota/lambda is a key effector of the PAR polarity complex which is considered a master determinant of apico-basal polarity in single-layered epithelial cells. In polarized epithelial cells aPKC is exquisitely localized by the PAR6 partner to a belt nearby the tight junctions. Surprisingly, tissue specific knock out of the transgenic floxed version with villin-CRE showed a chronic inflammation phenotype. The observations were made in three different independent transgenic mouse lines and published by three different groups including ours (PMID: 27226486; PMID: 30552022; PMID: 21744423 ), which is reassuring for reproducibility. An additional double KO in both aPKC isoforms further confirmed the results (PMID: 30552022 ). The animals were viable and there was not strong diarrheal or constipation phenotype characteristic of polarity defects in intestinal epithelia. With few exceptions such as ezrin localization, apical polarity markers were generally well polarized. There were changes in cytokine expression by epithelial cells and infiltration of CD8+ T cells (PMID: 27226486; PMID: 30552022). The goal of the study was to get an unbiased catalog of the transcriptional changes induced by aPKC iota/lambda defect in intestinal epithelial cells to understand the ontology of gene expression downstream of the PAR polarity complex. The results are consistent with broad changes in NF-kB and IFN dependent transcriptional pathways, possibly mediated by ROCK and Med17 downstream of aPKCiota/lambda (PMID: 2722648; PMID: 33596087). This study was published in PMID: 33596087.
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Project description:The Cre-driver system is used to generate conditional knockout mice. Tamoxifen inducible Cre-driver mice can be used for spatiotemporal knockout by administration of the drug. A major tamoxifen administration is performed by intraperitoneal administration or oral administration. However, these forced administrations may be damaging to mice. Herein, we have demonstrated an improved method of administering tamoxifen with powdered food to mice. A mouse line expressing the tamoxifen-inducible Cre gene was used ubiquitously in this experiment to evaluate the efficiency of Cre recombination in the whole body. Our method also achieved efficient recombination without causing injury to mice. The X-gal staining intensity of the feeding method was equivalent to that of the intraperitoneal administration method. Furthermore, this method can be used for recombination before birth, or during the fetal period. We recommend researchers to employ this feeding method to administer tamoxifen to minimize the risk of injury to mice.
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