Description: Das Projekt "Rolle von TNF a/b in der Toxizitaet" wird vom Umweltbundesamt gefördert und von Eidgenössische Technische Hochschule Zürich, Institut für Toxikologie durchgeführt. Exposure of animals to drugs at high doses or environmental toxins causes often weight loss, hypotension, anemia, acute phase reaction and tissue damage. The administration of recombinant tumor necrosis factor a (TNF alpha, also known as cachectin) in animals causes a similar toxic response pattern. Thus, it is hypothesized that toxicity may be due to the overproduction of endogenous TNF alpha, which functions as the central effector cytokine of a toxic response. The goals of the present investigations are to generate on the one hand mice deficient in TNF alpha and TNF alpha/beta and on the other hand a TNF alpha-lacZ reporter mouse. 1. In order to define the role of TNF alpha in mediating various aspects of general toxicity, mice with a disrupted TNF alpha gene will be generated. Since both TNF alpha and TNF beta are in close proximity on the genome and share some biological features such as common cell surface receptors, we consider the generation of a mouse with a deletion of both TNF genes. Homozygous off springs of both TNF alpha and TNF alpha/beta deleted chimeras should give conclusive information on the role of both gene products for toxicity. 2. In parallel to these delection mutants the generation of a TNF alpha-lacZ reporter mouse would allow for the rapid analysis of cell and tissue specific transcription of TNF alpha in a time dependent way after challenge with toxins. The combination of a fluorogenic beta-galactosidase assay with other cell specific fluorescence markers in cytofluorometry will provide a sophisticated tool to study TNF alpha induction.
Types:
SupportProgram
Origin: /Bund/UBA/UFORDAT
Tags: Fluoreszenz ? Gen ? Biopharmazeutikum ? Genom ? Mutation ? Zürich ? Arzneimittel ? DNA ? Genetik ? Schadstoffwirkung ? Tracer ? Staub ? Schwermetall ? Generationsdauer ? Akute Exposition ? Schaden durch Tiere ? Anfechtung ? Genotoxizität ? Maus ? Schadstoffexposition ? Therapie ? Toxin ? Umweltbelastung ? Metall ? Krebserkrankung ? Toxizität ? Tumor ? Tier ? Studie ? Tierversuch ? Toxikologie ? Ernährung ? Metal lourd / metal ? ADN ? Toxicite ? Tumor-Nekrose-Faktor ? Poussiere ? TNF ? TNF-alpha ?
License: cc-by-nc-nd/4.0
Language: Deutsch
Time ranges: 1992-07-01 - 2024-11-29
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