Objective
Mutations in WT1 result in different developmental abnormalities, among which is Wilms' tumor. Many different isoforms of the protein have been described, with different functions for at least some of them. However, many of the studies describing these differences have been in vitro experiments using artificial (over expression) situations. In this project we will analyze the phenotypical effects of limiting the number of different isoforms a cell can express through a genetically approach. Our main focus will be on two alternative splicing events in the gene, determining the use of exon 5 and the use of three additional amino acids (KTS), since disturbance of the ratio between expression levels of these variants is a potential inactivation mechanism of WT1 in malignancies. To study the different functions of these variants in a physiological context we will generate a high-efficiency system to manipulate the Wt1 gene in mouse ES cells . We intend to use a RMCF (recombines-mediated cassette exchange) approach, in which F1p-mediated recombination is used to transfer variant Wt1 genes from a BAC to the endogenous Wt1 locus. This system will be used to generate mouse models only expressing Wt1 variants with or without exon 5 for in vivo analysis. Additionally, variants with the four possible combinations of the exon 5 and KTS splice variants will be generated for extensive in vitro analysis in a molecular, biochemical and cell biological context.
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 biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics mutation
- natural sciences mathematics pure mathematics mathematical analysis functional analysis
- natural sciences chemical sciences organic chemistry amines
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Funding Scheme
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.
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
EH4 2XU EDINBURGH
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.