Search results for "Disease models"

Chemically induced mouse models of intestinal inflammation

2007

Animal models of intestinal inflammation are indispensable for our understanding of the pathogenesis of Crohn disease and ulcerative colitis, the two major forms of inflammatory bowel disease in humans. Here, we provide protocols for establishing murine 2,4,6-trinitro benzene sulfonic acid (TNBS)-, oxazolone- and both acute and chronic dextran sodium sulfate (DSS) colitis, the most widely used chemically induced models of intestinal inflammation. In the former two models, colitis is induced by intrarectal administration of the covalently reactive reagents TNBS/oxazolone, which are believed to induce a T-cell-mediated response against hapten-modified autologous proteins/luminal antigens. In …

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 …

Toward evidence-based severity assessment in rat models with repeated seizures: II. Chemical post-status epilepticus model.

2019

Objective: Considering the complexity of neuronal circuits and their epilepsy-associated alterations, epilepsy models cannot be completely replaced by in vitro experimental approaches. Decisions about ethical approval of in vivo studies require a thorough weighing of the animal's burden and the benefit regarding the expected gain in knowledge. Methods: Based on combined behavioral, biochemical, and physiological analyses, we assessed the impact on animal well-being and condition in different phases of the pilocarpine post–status epilepticus (SE) model in rats. Results: As a consequence of SE, increased levels of impairment were evident in the early postinsult phase and late chronic phase, w…

Haematopoietic stem cell transplantation in the treatment of autoimmune diseases: current experience from an international data base.

2000

Anesthesia for Euthanasia Influences mRNA Expression in Healthy Mice and after Traumatic Brain Injury

2014

Tissue sampling for gene expression analysis is usually performed under general anesthesia. Anesthetics are known to modulate hemodynamics, receptor-mediated signaling cascades, and outcome parameters. The present study determined the influence of anesthetic paradigms typically used for euthanization and tissue sampling on cerebral mRNA expression in mice. Naïve mice and animals with acute traumatic brain injury induced by controlled cortical impact (CCI) were randomized to the following euthanasia protocols (n=10-11/group): no anesthesia (NA), 1 min of 4 vol% isoflurane in room air (ISO), 3 min of a combination of 5 mg/kg midazolam, 0.05 mg/kg fentanyl, and 0.5 mg/kg medetomidine intraperi…

Does autoimmunity play a part in the pathogenesis of glaucoma?

2013

Glaucoma is a chronic neurodegenerative disease and one of the leading causes of blindness. Several risk factors have been described, e.g. an elevated intraocular pressure (IOP), oxidative stress or mitochondrial dysfunction. Additionally, alterations in serum antibody profiles of glaucoma patients, upregulation (e.g. anti-HSP60, anti-MBP) and downregulation (e.g. anti-14-3-3), have been described, but it still remains elusive if the autoantibodies seen in glaucoma are an epiphenomenon or causative. However, it is known that elicited autoimmunity causes retinal ganglion cell loss resulting in glaucomatous-like damage and according to the autoaggressive nature of some autoantibodies we found…

Instruction of haematopoietic lineage choices, evolution of transcriptional landscapes and cancer stem cell hierarchies derived from an AML1-ETO mous…

2013

The t(8;21) chromosomal translocation activates aberrant expression of the AML1-ETO (AE) fusion protein and is commonly associated with core binding factor acute myeloid leukaemia (CBF AML). Combining a conditional mouse model that closely resembles the slow evolution and the mosaic AE expression pattern of human t(8;21) CBF AML with global transcriptome sequencing, we find that disease progression was characterized by two principal pathogenic mechanisms. Initially, AE expression modified the lineage potential of haematopoietic stem cells (HSCs), resulting in the selective expansion of the myeloid compartment at the expense of normal erythro- and lymphopoiesis. This lineage skewing was foll…

Antioxidant compound supplementation prevents oxidative damage in a Drosophila model of Parkinson's disease

2013

Loss-of-function mutations in the DJ-1 gene are linked to rare autosomal recessive forms of parkinsonism. In Drosophila, two DJ-1 orthologs have been identified, DJ-1α and DJ-1β. Several studies have shown that DJ-1β mutant flies are viable and fertile but exhibit age-dependent locomotor defects, shortened life span, and enhanced sensitivity to toxins that induce oxidative stress response compared to control flies. We also demonstrated that long-term dietary supplementation with antioxidant compounds was effective at increasing life-span values of DJ-1β mutants. These results, together with high levels of oxidative stress markers detected in newly eclosed DJ-1β mutant flies compared to cont…

PCARE and WASF3 regulate ciliary F-actin assembly that is required for the initiation of photoreceptor outer segment disk formation

2020

Significance The photoreceptor outer segments are primary cilia, modified for phototransduction by incorporation of stacked opsin-loaded membrane disks that are continuously regenerated. This process is disrupted in several types of inherited retinal dystrophy, but the driving force remained unclear. We show that C2orf71/PCARE (photoreceptor cilium actin regulator), associated with inherited retinal dystrophy subtype RP54, efficiently recruits the Arp2/3 complex activator WASF3 to the cilium. This activates an actin dynamics-driven expansion of the ciliary tip, resembling membrane evagination in lamellipodia formation. Colocalization of this actin dynamics module to the base of the outer se…

Tissue‐dependent differences in Bardet–Biedl syndrome gene expression

2019

BACKGROUND INFORMATION Primary cilia are highly conserved multifunctional cell organelles that extend from the cell membrane. A range of genetic disorders, collectively termed ciliopathies, is attributed to primary cilia dysfunction. The archetypical ciliopathy is the Bardet-Biedl syndrome (BBS), patients of which display virtually all symptoms associated with dysfunctional cilia. The primary cilium acts as a sensory organelle transmitting intra- and extracellular signals thereby transducing various signalling pathways facilitated by the BBS proteins. Growing evidence suggests that cilia proteins also have alternative functions in ciliary independent mechanisms, which might be contributing …