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Third-party-funded project

Title:
Immunopathological Mechanisms in animal models of hereditary Neuropathies

Project management at the University of Würzburg:

Participating scientists:

Abstract:
We could demonstrate that in P0+- mice and also in Cx32-deficient mice, the primarily genetically-mediated demyelination is mediated by T-lymphocytes and macrophages (Schmid et al., 2000; Carenini et al., 2001; Mäurer et al., 2001; Kobsar et al., 2002b; Kobsar et al., 2002a).

Based on the observation that macrophages are the first cells in the mutant nerves that are activated and that this activation might be mediated by MCP-1 and M-CSF (Carenini et al., 2001) (and unpublished results) we want to investigate the intracellular signalling cascade which leads from the myelin mutation to the upregulation of the respective chemokines and cytokines. Candidates are the MAP-kinase pathway, the NFB/IB cascade and the PI-3-kinase/protein kinase B complex.

In another series of experiments, we would like to investigate whether CD4+ or CD8+ T-lymphocytes are involved in the immune-modulated demyelination in P0+- mice. For this purpose, lymphocyte-deficient P0+-/RAG-1-- mice will receive bone marrow from either CD4 knockout or CD8 knockout mice. The analysis of the resulting phenotypes will be instrumental in understanding the impact of the different types of T-lymphocytes. Furthermore, splenocytes of the bone-marrow chimeras will be investigated with regard of their capacity to recognize myelin-related antigens.

In a third project, both P0+- and Cx32 mutants will receive an immune thearpy which is based on prednisolon-containing liposomes that specifically lead to a downregulation of endoneurial macrophages.

Projekt period: from 07.2000 to 06.2003

Funding institution:
DFG ( SFB581 ) ,Granting date: 23.06.2000

Publications: