Reference:
GP0072Y01
Abstract:
Rett syndrome (RTT) is a genetic disease that occurs almost exclusively in females, with an estimated prevalence of 1 in 10.000-15.000 female births. After normal development up to the age of 6-18 months, follows a period of regression of motor and mental abilities. Affected patients develop loss of speech and purposeful hand use, autism and a profound mental handicap. Recently, the gene coding for MeCP2 has been identified as the molecular cause of RTT. MeCP2 is a trascriptional repressor that selectively binds to methylated DNA (the major covalent modification of mammalian genome). It has been hypothesized that the main function of this protein is to prevent unscheduled transcription throughout the genome. Not only many informations are still missing about the molecular mechanisms by which MeCP2 inhibits gene expression, but also the Rett syndrome is still very poorly characterized. In particular, we have to define if other mutated genes, apart from MeCP2, can determine this disease and we have to reveal other proteins that can influence the severity of the pathology. We believe that the identification of the molecular mechanisms by which MeCP2 inhibits gene expression and the identification of other proteins that participate to the same pathway of gene repression will permit to better characterize RTT and to develop diagnostic tests and therapeutic strategies. To this purpose, recently we have isolated three proteins that seem to work together with MeCP2. With this proposal we intend to isolate and characterize their coding genes, and to understand how these factors interact with MeCP2 and if this interactions are maintained with the RTT mutant forms of MeCP2. Finally, we want to comprehend the biological function of the isolated proteins and their possible contribution to this severe genetic disease.
PROJECT DETAILS
beginning: 2001.
end: 2004.
Country of research: Italy
Counry of funding source: Italy
Funding organization: Telethon
Financing: PRIVATE FUNDERS – 116 203 €