Search results for "Mouse models"
showing 10 items of 35 documents
The Microbiota Promotes Arterial Thrombosis in Low-Density Lipoprotein Receptor-Deficient Mice
2019
Our results demonstrate a functional role for the commensal microbiota in atherothrombosis. In a ferric chloride injury model of the carotid artery, GF C57BL/6J mice had increased occlusion times compared to colonized controls. Interestingly, in late atherosclerosis, HFD-fed GF Ldlr−/− mice had reduced plaque rupture-induced thrombus growth in the carotid artery and diminished ex vivo thrombus formation under arterial flow conditions.
AAV-Mediated Clarin-1 Expression in the Mouse Retina: Implications for USH3A Gene Therapy
2015
Usher syndrome type III (USH3A) is an autosomal recessive disorder caused by mutations in clarin-1 (CLRN1) gene, leading to progressive retinal degeneration and sensorineural deafness. Efforts to develop therapies for preventing photoreceptor cell loss are hampered by the lack of a retinal phenotype in the existing USH3 mouse models and by conflicting reports regarding the endogenous retinal localization of clarin-1, a transmembrane protein of unknown function. In this study, we used an AAV-based approach to express CLRN1 in the mouse retina in order to determine the pattern of its subcellular localization in different cell types. We found that all major classes of retinal cells express AAV…
Different behavior of myeloperoxidase in two rodent amoebic liver abscess models.
2016
The protozoan Entamoeba histolytica is the etiological agent of amoebiasis, which can spread to the liver and form amoebic liver abscesses. Histological studies conducted with resistant and susceptible models of amoebic liver abscesses (ALAs) have established that neutrophils are the first cells to contact invasive amoebae at the lesion site. Myeloperoxidase is the most abundant enzyme secreted by neutrophils. It uses hydrogen peroxide secreted by the same cells to oxidize chloride ions and produce hypochlorous acid, which is the most efficient microbicidal system of neutrophils. In a previous report, our group demonstrated that myeloperoxidase presents amoebicidal activity in vitro. The ai…
The actin remodeling protein cofilin is crucial for thymic αβ but not γδ T-cell development
2018
Cofilin is an essential actin remodeling protein promoting depolymerization and severing of actin filaments. To address the relevance of cofilin for the development and function of T cells in vivo, we generated knock-in mice in which T-cell–specific nonfunctional (nf) cofilin was expressed instead of wild-type (WT) cofilin. Nf cofilin mice lacked peripheral αβ T cells and showed a severe thymus atrophy. This was caused by an early developmental arrest of thymocytes at the double negative (DN) stage. Importantly, even though DN thymocytes expressed the TCRβ chain intracellularly, they completely lacked TCRβ surface expression. In contrast, nf cofilin mice possessed normal numbers of γδ T cel…
Humanization of the Blood-Brain Barrier Transporter ABCB1 in Mice Disrupts Genomic Locus - Lessons from Three Unsuccessful Approaches
2018
ATP-binding cassette (ABC) transporters are of major importance for the restricted access of toxins and drugs to the human body. At the body's barrier tissues like the blood-brain barrier, these transporters are highly represented. Especially, ABCB1 (P-glycoprotein) has been a priority target of pharmaceutical research, for instance, to aid chemotherapy of cancers, therapy resistant epilepsy, and lately even neurodegenerative diseases. To improve translational research, the humanization of mouse genes has become a popular tool although, like recently seen for Abcb1, not all approaches were successful. Here, we report the characterization of another unsuccessful commercially available ABCB1 …
Delivery of epirubicin via slow infusion as a strategy to mitigate chemotherapy-induced cardiotoxicity
2017
Background Continuous infusion of doxorubicin has been a strategy to reduce cardiotoxicity. Epirubicin is another anthracycline in common clinical use. However, evidence is lacking regarding whether this strategy can reduce cardiotoxicity of epirubicin without compromising antineoplastic efficacy. Design and methods Healthy rats were randomized into groups: epirubicin (8 mg/kg) delivered intraperitoneally via micro osmotic pumps (MOP), epirubicin (8 mg/kg) by intraperitoneal (IP) bolus injection, and placebo control. Blood samples were collected for analyzing biomarkers of myocardial injury and pharmacokinetics. At chosen times, sub-groups of animals were sacrificed for histopathology. A mo…
Mouse models of multiple myeloma: technologic platforms and perspectives.
2018
Murine models of human multiple myeloma (MM) are key tools for the study of disease biology as well as for investigation and selection of novel candidate therapeutics for clinical translation. In the last years, a variety of pre-clinical models have been generated to recapitulate a wide spectrum of biological features of MM. These systems range from spontaneous or transgenic models of murine MM, to subcutaneous or orthothopic xenografts of human MM cell lines in immune compromised animals, to platform allowing the engraftment of primary/bone marrow-dependent MM cells within a human bone marrow milieu to fully recapitulate human disease. Selecting the right model for specific pre-clinical re…
A conditional inducible JAK2V617F transgenic mouse model reveals myeloproliferative disease that is reversible upon switching off transgene expressio…
2019
Aberrant activation of the JAK/STAT pathway is thought to be the critical event in the pathogenesis of the chronic myeloproliferative neoplasms, polycythemia vera, essential thrombocythemia and primary myelofibrosis. The most frequent genetic alteration in these pathologies is the activating JAK2V617F mutation, and expression of the mutant gene in mouse models was shown to cause a phenotype resembling the human diseases. Given the body of genetic evidence, it has come as a sobering finding that JAK inhibitor therapy only modestly suppresses the JAK2V617F allele burden, despite showing clear benefits in terms of reducing splenomegaly and constitutional symptoms in patients. To gain a better …
Rapid nucleus-scale reorganization of chromatin in neurons enables transcriptional adaptation for memory consolidation
2020
AbstractThe interphase nucleus is functionally organized in active and repressed territories defining the transcriptional status of the cell. However, it remains poorly understood how the nuclear architecture of neurons adapts in response to behaviorally relevant stimuli that trigger fast alterations in gene expression patterns. Imaging of fluorescently tagged nucleosomes revealed that pharmacological manipulation of neuronal activity in vitro and auditory cued fear conditioning in vivo induce nucleus-scale restructuring of chromatin within minutes. Furthermore, the acquisition of auditory fear memory is impaired after infusion of a drug into auditory cortex which blocks chromatin reorganiz…
With mouse age comes wisdom : a review and suggestions of relevant mouse models for age-related conditions
2016
Ageing is a complex multifactorial process that results in many changes in physiological changes processes that ultimately increase susceptibility to a wide range of diseases. As such an ageing population is resulting in a pressing need for more and improved treatments across an assortment of diseases. Such treatments can come from a better understanding of the pathogenic pathways which, in turn, can be derived from models of disease. Therefore the more closely the model resembles the disease situation the more likely relevant the data will be that is generated from them. Here we review the state of knowledge of mouse models of a range of diseases and aspects of an ageing physiology that ar…