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Effect of conditional knockout of Prkci (atypical PKC iota/lambda coding gene) in mouse enterocytes reveals robust innate immunity transcriptomic response

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE235056 | GEO | 2023/06/15

REPOSITORIES: GEO

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