Objective
Tat1 (SLC26A8) encodes for an anionic exchanger exclusively expressed at the plasma membrane of human adult germ cells undergoing spermatogenesis. Although so far the physiological role of this molecule is unknown, it has been shown to transport sulphate i n a chloride dependant manner and it is likely to fulfil critical functions during spermatogenesis. Indeed, Tat1 belongs to a family of transporters, which physiological importance has been clearly demonstrated by association with several human disorders ( Pendred syndrome, Dyastrophic dysplasia, Congenital chloride diarrhoea). Furthermore, Tat1 regulate the transport of sulphate that we know is essential for many biological processes (i.e growth, development). For instance, hyposulphation of the proteoglycans located in the extra-cellular matrix of the cartilage, leads to dramatic bone development defects in patients diagnosed for Dyastrophic dysplasia. In order to define the physiological function of Tat1 we propose to use an RNAi based methodology to specifically down-regulate Tat1 expression in the adult mouse testis. We will take advantage of a new expression vector designed to produce siRNA-like transcripts that can specifically initiate degradation of the endogenous mRNA to which they are homologous. We propose to generate transgenic mice with constructs producing Tat1 siRNA molecules, and therefore down-regulate Tat1 expression in the appropriated tissues (so far Tat1 has been shown to be solely expressed in the adult testis). In parallel, we will elect roporate the expression vector into adult mouse testis in order to locally inhibit Tat1 expression. Combination of these two approaches should allow characterisation of the potential spermatogenesis defects associated with the lack of Tat1 activity. Subsequent search for similar abnormalities in human infertile patients will permit to investigate Tat1 implication in the aetiology of this disorder.
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.
- medical and health sciences clinical medicine andrology
- social sciences sociology demography fertility
- natural sciences biological sciences genetics mutation
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2002-MOBILITY-11
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Funding Scheme
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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
PARIS
France
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