Effect of doxycycline treatment on germ-free mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE202754 | GEO | 2022/09/14
REPOSITORIES: GEO
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Project description:Abstract: Many mouse models of neurological disease use the tetracycline transactivator (tTA) system to control transgene expression by oral treatment with the broad-spectrum antibiotic doxycycline. Antibiotic treatment used for transgene control might have undesirable systemic effects, including the potential to affect immune responses in the brain via changes in the gut microbiome. Recent work has shown that an antibiotic cocktail to perturb the gut microbiome can suppress microglial reactivity to brain amyloidosis in transgenic mouse models of Alzheimer's disease based on controlled overexpression of the amyloid precursor protein (APP). Here we assessed the impact of chronic low dose doxycycline on gut microbiome diversity and neuroimmune response to systemic LPS challenge in a tTA-regulated model of Alzheimer's amyloidosis. We show that doxycycline decreased microbiome diversity in both APP transgenic and wild-type mice and that these changes persisted long after drug withdrawal. Despite this change in microbiome composition, dox treatment had minimal effect on transcriptional signatures in the brain, both at baseline and following acute LPS challenge. Our findings suggest that central neuroinflammatory responses may be less affected by dox at doses needed for transgene control than by antibiotic cocktail at doses used for microbiome manipulation.
2024-01-10 | GSE236242 | GEO
Project description:To determine the genes responsive to FfmA in A. fumigatus, a doxycycline-repressible (dox off) gene fusion to the ffmA coding sequence was constructed. This strain was designated SPF182. These cells were grown for 16 hours in the absence of doxycycline and then shifted into medium containing doxycycline (+dox) or untreated (-dox). After 8 additional hours, the cells were harvested and total RNA prepared. Wild-type cells were grown in parallel as a control in -dox medium.
2023-07-26 | GSE229912 | GEO
Project description:Ischemia/reperfusion injury (IRI) is a hallmark of tissue injury in donation after circulatory death (DCD) kidneys. The implementation of hypothermic machine perfusion (HMP) provides a platform for repair of DCD kidneys. Doxycycline administration has shown protective effects during IRI. Here, we explore the impact of doxycycline on proteolytic degradation mechanisms and the urinary proteome of perfused kidney grafts. Porcine kidneys underwent 30 min of warm ischemia, 24 h of oxygenated HMP (control/doxycycline) and 240 min of ex-vivo reperfusion. A high-efficiency undecanal-based N-termini enrichment workflow (HUNTER) was performed to identify the tissue degradome. In addition, a proteomic analysis was applied on urine samples collected during reperfusion using label-free quantitation (LFQ) mass spectrometry. Hierarchical clustering showed distinctive clustering profiles between urine samples collected at T15 min (metabolism) and T240 min (complement and coagulation). At T10, significantly more degraded proteins were observed in perfusates of the control group. At T240, significantly more degraded proteins were observed in the doxycycline group, indicating that doxycycline alters protein degradation during HMP. In conclusion, doxycycline administration during HMP led to significant proteomic differences including protective effects by attenuating urinary NGAL levels. Ultimately, we unravelled multiple pathways that undergo alterations during machine perfusion that can be targeted to attenuate IRI induced injury.
2022-08-12 | PXD029599 | Pride
Project description:We overexpressed YAP in the intestinal epithelium by adding doxycycline to the drinking water of experimental mice. Mice were given dox for 2 days, and referred to as Tg (transgenic).
2012-11-29 | GSE41506 | GEO
Project description:The tetracycline antibiotics are widely used in biomedical research as mediators of inducible gene expression systems. Despite many known effects of tetracyclines on mammalian cells -- including inhibition of the mitochondrial ribosome -- there have been few reports on potential off-target effects at concentrations commonly used in inducible systems. Here, we report that in human cell lines, commonly used concentrations of doxycycline change gene expression patterns and concomitantly shift metabolism towards a more glycolytic phenotype, evidenced by increased lactate secretion and reduced oxygen consumption. We also show that these concentrations are sufficient to slow proliferation and alter cell cycle progression in vitro. These findings suggest that researchers using doxycycline in inducible expression systems should design appropriate controls to account for potential confounding effects of the drug on cellular metabolism. Total RNA was extracted from MCF12A cells treated with either vehicle control or Dox at 1 ug/mL. The experiment was performed in biological triplicate. Microarray results were processed using the RMA method.
2013-04-22 | E-GEOD-45029 | biostudies-arrayexpress
Project description:Mice with mitochondrial complex I deficiency (Ndufs4-/-) suffer from severe energy impairment primarily affecting the brain and die at P55. A small molecule screen developed by our lab using cells harboring human mitochondrial disease mutations identified antibiotics targeting mitochondrial translation as potent inhibitors of cell death under nutrient stress conditions. Doxycycline, which was identified amongst these antibiotics, was administered in the diet of Ndufs4-/- mice after weaning at P21. Mice fed with doxycycline showed improved motor function and significantly increased lifespan relative to untreated Ndufs4-/- mice. In order to investigate the molecular changes promoted by doxycycline in the brains of these mice, Ndufs4-/- doxycycline treated (DOX), Ndufs4-/- untreated (KO), and Ndufs4+/+ (WT) control mice were sacrificed at P55 and their brains harvested. Proteomic analysis revealed doxycycline treatment largely prevented the neuroimmune and inflammatory profile identified in the Ndufs4-/- mice. These findings implicate a potentially causality of these proteins in the neuronal cell death ultimately leading to the observed brain pathology.
2021-09-09 | PXD022860 | Pride
Project description:The microbiome has been shown to have significant effects on susceptibility to liver disease. How the microbiome affects hepatic signaling pathways to mechanistically mediate these responses is unknown. Utilizing germ-free and conventionalized (microbiome-replete) mice, we characterized the effects of having a microbiome on the hepatic transcriptome.
2020-02-11 | GSE145012 | GEO
Project description:We overexpressed YAP in the intestinal epithelium by adding doxycycline to the drinking water of experimental mice. Mice were given dox for 2 days, and referred to as Tg (transgenic). Mice were given dox for 2 days, sacrificed, and crypts were isolated for RNA extraction and analyzed by Affymetrix microarrays.
2012-11-29 | E-GEOD-41506 | biostudies-arrayexpress
Project description:The tetracycline antibiotics are widely used in biomedical research as mediators of inducible gene expression systems. Despite many known effects of tetracyclines on mammalian cells -- including inhibition of the mitochondrial ribosome -- there have been few reports on potential off-target effects at concentrations commonly used in inducible systems. Here, we report that in human cell lines, commonly used concentrations of doxycycline change gene expression patterns and concomitantly shift metabolism towards a more glycolytic phenotype, evidenced by increased lactate secretion and reduced oxygen consumption. We also show that these concentrations are sufficient to slow proliferation and alter cell cycle progression in vitro. These findings suggest that researchers using doxycycline in inducible expression systems should design appropriate controls to account for potential confounding effects of the drug on cellular metabolism.
2013-04-22 | GSE45029 | GEO
Project description:double transgenic mice (tTA/IkappaBalpha-AA) were treated with doxycycline (DOX), which represses expression of the transgenic IkappaBalpha. Double transgenic mice without Dox-treatment overexpress the transdominant IkappaBalpha, which represses NFkappaB activation.
2006-05-10 | E-MEXP-358 | biostudies-arrayexpress