Search results for "Knockout mouse"

Erythropoietin mediates tissue protection through an erythropoietin and common beta-subunit heteroreceptor

2004

The cytokine erythropoietin (Epo) is tissue-protective in preclinical models of ischemic, traumatic, toxic, and inflammatory injuries. We have recently characterized Epo derivatives that do not bind to the Epo receptor (EpoR) yet are tissue-protective. For example, carbamylated Epo (CEpo) does not stimulate erythropoiesis, yet it prevents tissue injury in a wide variety ofin vivoandin vitromodels. These observations suggest that another receptor is responsible for the tissue-protective actions of Epo. Notably, prior investigation suggests that EpoR physically interacts with the common β receptor (βcR), the signal-transducing subunit shared by the granulocyte-macrophage colony stimulating fa…

Smad7 controls resistance of colitogenic T cells to regulatory T cell-mediated suppression.

2008

Background & Aims Foxp3-expressing regulatory T cells (Tregs) play a key role in the maintenance of the gut immune homeostasis, and an intact transforming growth factor (TGF)-β signaling is required for their function. In inflammatory bowel disease (IBD), the TGF-β signaling is impaired because of high expression of the inhibitory molecule Smad7. Although no intrinsic defects in Tregs function have been shown in IBD, it is still unknown whether colitogenic T cells are susceptible to Treg-mediated suppression. In this study, we have investigated whether IBD mucosal CD4+ T cells are resistant to Tregs and whether Smad7 is involved in this process. Methods IBD lamina propria mononuclear cells …

Knock out der c-Jun N-terminalen Kinase 2 (JNK2) aggraviert die Entwicklung der chronischen DSS-Colitis unabhängig von der intestinalen Zytokin-Expre…

2008

Background The c-Jun N-terminal kinase 2 (JNK2) is involved in signal transduction of inflammatory bowel diseases (IBD) and regulates the expression of pro-inflammatory cytokines. For this reason, JNK2 is considered as novel target for IBD therapy. The aim of this study was 1.) to examine the function of JNK2 applying a low dose Dextran Sulfate Sodium (DSS) model of chronic experimental colitis in JNK2 knock out mice and 2.) to analyze the expression of JNK2 dependent cytokines. Material and Methods: For induction of a mild chronic colitis, female JNK2 knockout mice (JNK2 ko) and their wildtype controls (WT2) received three cycles of DSS treatment, each consisting of 1.0 % DSS for 5 days, f…

C1 Inhibitor-C1¯sComplexes Are Internalized and Degraded by the Low Density Lipoprotein Receptor-related Protein

1997

Like other serpin-enzyme complexes (SECs), proteinase-complexed C1 inhibitor (C1-INH) is rapidly cleared from the circulation and thought to be a neutrophil chemoattractant, suggesting that complex formation causes structural rearrangements exposing a domain which is recognized by specific cell surface receptors. However, the cellular receptor(s) responsible for the catabolism and potential mediation of chemotaxis by C1-INH-protease complexes remained obscure. To determine whether the SEC receptor mediates the binding and potential chemotaxis of C1-INH·C1s, we performed binding assays with HepG2 cells, neutrophils, and monocytes, and the results show that C1-INH·C1s neither bind to these ce…

Generation and functional analyses of hepatocyte-specific type I interleukin-1 receptor (IL-1RI) knockout mice

2016

P087 Increased wnt ligands expression in M2c macrophages is associated with fibrosis in Stat6 knockout mice

2017

Genetic Deletion of JNK1 and JNK2 Aggravates the DSS-Induced Colitis in Mice

2007

The c-Jun N-terminal kinases (JNKs) are considered as novel targets for therapy of inflammatory bowel diseases (IBD). However, the relevant JNK isoforms have to be elucidated. Here, we analyze the individual contribution of the JNK1 and JNK2 isoforms in a dextran sulfate sodium (DSS) model of experimental colitis. JNK1 and JNK2 knockout mice (JNK1 ko, JNK2 ko) and their wild-type controls (WT1, WT2) received three cycles of DSS treatment, each consisting of 1.7% DSS for 5 days, followed by 5 days with water. Animals were daily evaluated by a disease activity index (DAI) comprising measurement of body weight, estimation of stool consistency, and test for occult blood/gross rectal bleeding. A…

Perivascular nerve fiber α-synuclein regulates contractility of mouse aorta: A link to autonomic dysfunction in Parkinson's disease

2010

Parkinson's disease and other neurodegenerative disorders associated to changes in alpha-synuclein often result in autonomic dysfunction, most of the time accompanied by abundant expression of this synaptic protein in peripheral autonomic neurons. Given that expression of alpha-synuclein in vascular elements has been previously reported, the present study was undertaken to determine whether alpha-synuclein directly participates in the regulation of vascular responsiveness. We detected by immunohistochemistry perivascular nerve fibers containing alpha-synuclein in the aorta of mice while aortic endothelial cells and muscular fibers themselves did not exhibit detectable levels of this protein…

p53 Involvement in the control of murine hair follicle regression.

2001

p53 is a transcription factor mediating a variety of biological responses including apoptotic cell death. p53 was recently shown to control apoptosis in the hair follicle induced by ionizing radiation and chemotherapy, but its role in the apoptosis-driven physiological hair follicle regression (catagen) remains to be elucidated. Here, we show that p53 protein is strongly expressed and co-localized with apoptotic markers in the regressing hair follicle compartments during catagen. In contrast to wild-type mice, p53 knockout mice show significant retardation of catagen accompanied by significant decrease in the number of apoptotic cells in the hair matrix. Furthermore, p53 null hair follicles…

Abnormal development of pacinian corpuscles in double trkB;trkC knockout mice.

2006

Pacinian corpuscles depend on either Aalpha or Abeta nerve fibers of the large- and intermediate-sized sensory neurons for the development and maintenance of the structural integrity. These neurons express TrkB and TrkC, two members of the family of signal transducing neurotrophin receptors, and mice lacking TrkB and TrkC lost specific neurons and the sensory corpuscles connected to them. The impact of single or double targeted mutations in trkB and trkC genes in the development of Pacinian corpuscles was investigated in 25-day-old mice using immunohistochemistry and ultrastructural techniques. Single mutations on trkB or trkC genes were without effect on the structure and S100 protein expr…