ArticlePloS one2012
Cre-mediated stress affects sirtuin expression levels, peroxisome biogenesis and metabolism, antioxidant and proinflammatory signaling pathways.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 39 citations in OpenAlex.
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- High-throughput mapping of single-neuron projection and molecular features by retrograde barcoded labeling.eLife · 2024Article
- Epigenetic dosage identifies two major and functionally distinct β cell subtypes.Cell metabolism · 2023Article
- Mouse Models to Study Peroxisomal Functions and Disorders: Overview, Caveats, and Recommendations.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Cre toxicity in mouse models of cardiovascular physiology and disease.Nature cardiovascular research · 2022Article
- Article
- A defect in the peroxisomal biogenesis in germ cells induces a spermatogenic arrest at the round spermatid stage in mice.Scientific reports · 2019Article
- Silencing ofJournal of Cancer · 2017Article
- C22-bronchial and T7-alveolar epithelial cell lines of the immortomouse are excellent murine cell culture model systems to study pulmonary peroxisome biology and metabolism.Histochemistry and cell biology · 2016Article
- Down, But Not Out: Partial Elimination of Androgen Receptors in the Male Mouse Brain Does Not Affect Androgenic Regulation of Anxiety or HPA Activity.Endocrinology · 2016Article
- Transfection of Sertoli cells with androgen receptor alters gene expression without androgen stimulation.BMC molecular biology · 2015Article
- Bladder function in mice with inducible smooth muscle-specific deletion of the manganese superoxide dismutase gene.American journal of physiology. Cell physiology · 2015Article
- MZB1 is a GRP94 cochaperone that enables proper immunoglobulin heavy chain biosynthesis upon ER stress.Genes & development · 2014Article
- mTOR plays a critical role in p53-induced oxidative kidney cell injury in HIVAN.American journal of physiology. Renal physiology · 2013Article
- Resveratrol: why is it a promising therapy for chronic kidney disease patients?Oxidative medicine and cellular longevity · 2013Review
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cre-mediated excision of loxP sites is widely used in mice to manipulate gene function in a tissue-specific manner. To analyze phenotypic alterations related to Cre-expression, we have used AMH-Cre-transgenic mice as a model system. Different Cre expression levels were obtained by investigation of C57BL/6J wild type as well as heterozygous and homozygous AMH-Cre-mice. Our results indicate that Cre-expression itself in Sertoli cells already has led to oxidative stress and lipid peroxidation (4-HNE lysine adducts), inducing PPARα/γ, peroxisome proliferation and alterations of peroxisome biogenesis (PEX5, PEX13 and PEX14) as well as metabolic proteins (ABCD1, ABCD3, MFP1, thiolase B, catalase). In addition to the strong catalase increase, a NRF2- and FOXO3-mediated antioxidative response (HMOX1 of the endoplasmic reticulum and mitochondrial SOD2) and a NF-κB activation were noted. TGFβ1 and proinflammatory cytokines like IL1, IL6 and TNFα were upregulated and stress-related signaling pathways were induced. Sertoli cell mRNA-microarray analysis revealed an increase of TNFR2-signaling components. 53BP1 recruitment and expression levels for DNA repair genes as well as for p53 were elevated and the ones for related sirtuin deacetylases affected (SIRT 1, 3-7) in Sertoli cells. Under chronic Cre-mediated DNA damage conditions a strong downregulation of Sirt1 was observed, suggesting that the decrease of this important coordinator between DNA repair and metabolic signaling might induce the repression release of major transcription factors regulating metabolic and cytokine-mediated stress pathways. Indeed, caspase-3 was activated and increased germ cell apoptosis was observed, suggesting paracrine effects. In conclusion, the observed wide stress-induced effects and metabolic alterations suggest that it is essential to use the correct control animals (Cre/Wt) with matched Cre expression levels to differentiate between Cre-mediated and specific gene-knock out-mediated effects.
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