Objective
We have previously found that ADAM 12 (A Disintegrin And Metalloprotease) can provoke myogenesis and is upregulated during muscle regeneration, but the mechanisms involved are unknown. We have generated transgenic mice over expressing ADAM 12 and bred them to mdx mice, which are the animal model for Duchenne muscular dystrophy. Interestingly, we found a significantly decreased degree of muscle cell necrosis and a decreased level of serum creatine kinase in these ADAM 12/mdx mice compared to mdx mice. Based on these striking results / we are interested in identifying molecular pathways by which ADAM 12 is implicated in myogenesis and muscle regeneration. For this purpose we will use the microarray technology to study the expression profile of 12000 genes in normal, ADAM 12 transgeneic, mdx, and mdx/ADAM 12 transgenic mice. Genes which expression is significantly modulated will be classified in functional clusters, which should give rise to different hypotheses concerning the molecular pathways of ADAM 12 action in muscle regeneration. We will then use different functional assays to test these hypotheses. Based on our preliminary results, we hypothesize that ADAM12 might contribute to muscle cell survival by playing an anti-apoptotic role. To test this hypothesis we will first focus on the analysis of calcium signaling which is known to be implicated in anti-apoptotic signals. As the analysis of the modulated genes goes on, other hypotheses might rise and will be tested.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences chemical sciences inorganic chemistry alkaline earth metals
- medical and health sciences basic medicine neurology muscular dystrophies duchenne muscular dystrophy
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
1017 KOEBENHAVN K/COPENHAEGEN
Denmark
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