Search results for "Knockout"
showing 10 items of 806 documents
Mast cell-derived tumour necrosis factor is essential for allergic airway disease
2007
Mast cells are thought to contribute to allergic airway disease. However, the role of mast cell-produced mediators, such as tumour necrosis factor (TNF), for the development of allergic airway disease is unclear. In order to define the role of mast cells in acute allergic airway disease two strains of mast cell-deficient mice (Kit W/Wv and Kit W-sh/W-sh ) were studied. Compared with their wild-type littermates, Kit W/Wv and Kit W-sh/W-sh mice developed significantly lower airway responsiveness to methacholine and less airway inflammation and goblet cell metaplasia, following sensitisation in the absence of adjuvant and airway challenge. Transfer of bone marrow-derived mast cells (BMMCs) fro…
Telomerase and Telomere Length in Pulmonary Fibrosis
2013
In addition to its expression in stem cells and many cancers, telomerase activity is transiently induced in murine bleomycin (BLM)-induced pulmonary fibrosis with increased levels of telomerase transcriptase (TERT) expression, which is essential for fibrosis. To extend these observations to human chronic fibrotic lung disease, we investigated the expression of telomerase activity in lung fibroblasts from patients with interstitial lung diseases (ILDs), including idiopathic pulmonary fibrosis (IPF). The results showed that telomerase activity was induced in more than 66% of IPF lung fibroblast samples, in comparison with less than 29% from control samples, some of which were obtained from lu…
Age-related and tissue-specific accumulation of oxidative DNA base damage in 7,8-dihydro-8-oxoguanine-DNA glycosylase (Ogg1) deficient mice.
2001
Mutations that influence the repair of oxidative DNA modifications are expected to increase the steady-state (background) levels of these modifications and thus create a mutator phenotype that predisposes to malignant transformation. We have analysed the steady-state levels and repair kinetics of oxidative DNA modifications in cells of homozygous ogg1(-/-) null mice, which are deficient in Ogg1 protein, a DNA repair glycosylase that removes the miscoding base 8-hydroxyguanine (8-oxoG) from the genome. Oxidative purine modifications including 8-oxoG were quantified by means of an alkaline elution assay in combination with Fpg protein, the bacterial functional analogue of Ogg1 protein. In pri…
Amyloid Beta-Mediated Changes in Synaptic Function and Spine Number of Neocortical Neurons Depend on NMDA Receptors
2021
Onset and progression of Alzheimer’s disease (AD) pathophysiology differs between brain regions. The neocortex, for example, is a brain region that is affected very early during AD. NMDA receptors (NMDARs) are involved in mediating amyloid beta (Aβ) toxicity. NMDAR expression, on the other hand, can be affected by Aβ. We tested whether the high vulnerability of neocortical neurons for Aβ-toxicity may result from specific NMDAR expression profiles or from a particular regulation of NMDAR expression by Aβ. Electrophysiological analyses suggested that pyramidal cells of 6-months-old wildtype mice express mostly GluN1/GluN2A NMDARs. While synaptic NMDAR-mediated currents are unaltered in 5xFAD …
EBV-Induced Gene 3 Transcription Is Induced by TLR Signaling in Primary Dendritic Cells via NF-κB Activation
2005
Abstract The EBV-induced gene 3 (EBI3) is expressed in dendritic cells (DCs) and part of the cytokine IL-27 that controls Th cell development. However, its regulated expression in DCs is poorly understood. In the present study we demonstrate that EBI3 is expressed in splenic CD8−, CD8+, and plasmacytoid DC subsets and is induced upon TLR signaling. Cloning and functional analysis of the EBI3 promoter using in vivo footprinting and mutagenesis showed that stimulation via TLR2, TLR4, and TLR9 transactivated the promoter in primary DCs via NF-κB and Ets binding sites at −90 and −73 bp upstream of the transcriptional start site, respectively. Furthermore, we observed that NF-κB p50/p65 and PU.1…
Age-dependent regulation of antioxidant genes by p38α MAPK in the liver
2018
p38α is a redox sensitive MAPK activated by pro-inflammatory cytokines and environmental, genotoxic and endoplasmic reticulum stresses. The aim of this work was to assess whether p38α controls the antioxidant defense in the liver, and if so, to elucidate the mechanism(s) involved and the age-related changes. For this purpose, we used liver-specific p38α-deficient mice at two different ages: young-mice (4 months-old) and old-mice (24 months-old). The liver of young p38α knock-out mice exhibited a decrease in GSH levels and an increase in GSSG/GSH ratio and malondialdehyde levels. However, old mice deficient in p38α had higher hepatic GSH levels and lower GSSG/GSH ratio than young p38α knock-…
The Miniball spectrometer
2013
The Miniball germanium detector array has been operational at the REX (Radioactive ion beam EXperiment) post accelerator at the Isotope Separator On-Line facility ISOLDE at CERN since 2001. During the last decade, a series of successful Coulomb excitation and transfer reaction studies have been performed with this array, utilizing the unique and high-quality radioactive ion beams which are available at ISOLDE. In this article, an overview is given of the technical details of the full Miniball setup, including a description of the γ-ray and particle detectors, beam monitoring devices and methods to deal with beam contamination. The specific timing properties of the REX-ISOLDE facility are hi…
Papel de hemo oxigensa-1 en la artritis inducida por transferencia de suero K/BxN. Caracterización del modelo experimental
2017
La Artritis Reumatoide (AR) es una enfermedad sistémica, crónica y de carácter autoinmune que produce daño articular en los pacientes. Cursa con la degradación del hueso subcondral y del cartílago articular causando un gran dolor; además de ser una enfermedad incapacitante, puede provocar síntomas extraarticulares que afecten a otros órganos. El estudio de la patogenia y del tratamiento de la AR se desarrolla en gran medida sobre modelos animales de artritis experimental. En la actualidad existen varios modelos de artritis en ratón ampliamente utilizados como son el modelo de Artritis Inducida por Colágeno (CIA) y el modelo por transferencia de suero K/BxN. Aunque ambos son de gran utilidad…
Erbb2 regulates neuromuscular synapse formation and is essential for muscle spindle development
2003
Neuregulins and their Erbb receptors have been implicated in neuromuscular synapse formation by regulating gene expression in subsynaptic nuclei. To analyze the function of Erbb2 in this process, we have inactivated the Erbb2 gene in developing muscle fibers by Cre/Lox-mediated gene ablation. Neuromuscular synapses form in the mutant mice, but the synapses are less efficient and contain reduced levels of acetylcholine receptors. Surprisingly, the mutant mice also show proprioceptive defects caused by abnormal muscle spindle development. Sensory Ia afferent neurons establish initial contact with Erbb2-deficient myotubes. However, functional spindles never develop. Taken together, our data su…
Second-generation Langerhans cells originating from epidermal precursors are essential for CD8+ T cell priming.
2014
Abstract In vivo studies questioned the ability of Langerhans cells (LCs) to mediate CD8+ T cell priming. To address this issue, we used intradermal immunization with plasmid DNA, a system in which activation of CD8+ T cells depends on delayed kinetics of Ag presentation. We found that dendritic cells (DCs) located in the skin at the time of immunization have limited ability to activate CD8+ T cells. This activity was mediated by a second generation of DCs that differentiated in the skin several days after immunization, as well as by lymph node–resident DCs. Intriguingly, CD8+ T cell responses were not affected following treatment with clodronate liposomes, immunization of CCR2−/− mice, or …