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Characterisation of immune response in mice expressing dream dominant negative

Objective

The Naranjo's group identified a new transcriptional repressor, named DREAM (Downstream Regulator Element Antagonist Modulator) that binds a region DRE located downstream from TATA box in target genes. This transcriptional repressor is expressed in brain, thymus, thyroid gland and testis and the repression is relieved by PKA- and calcium-dependent pathways. The goal of this project is to determine the function of DREAM in T cells by using transgenic mice expressing dominant negative mutants of DREAM. The Ick promoter is used to drive T cell-specific expression of the transgene. I shall characterize the phenotype of transgenic mice by studying T cell development in thymus: the number of T cells and the expression of various surface markers will be compared between wild-type, heterozygous and homozygous littermates. The effect of DREAM on negative and positive selection of thymocytes will be also investigated. We expect defective T cell ontogeny in transgenic mice. In order to evaluate the function of T cells at the periphery, we plan to use the Tet-off system. The capacity of transgenic mice to mount a proper immune response after immunization will be studied in mice supplemented with tetracycline. Since the expression of FasL and Hrk is controlled by DREAM, the effect of dominant negative mutants of DREAM on apoptotic process will be particularly assessed.

Funding Scheme

RGI - Research grants (individual fellowships)

Coordinator

CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Address
Campus De Cantoblanco
28049 Madrid
Spain