Reference:
GGP13187
Abstract:
Rett syndrome (RS) is a disease of the nervous system that manifests itself in baby girls at about 6-18 months of age. It is characterized by the onset of a complex set of neurological signs, including mental retardation, autism, epilepsy. In most cases RS is caused by the loss of function of the gene that express he protein MeCP2 localized on the X chromosome. We know that MeCP2 regulates gene expression and DNA structure and that it is essential for the correct development of the nervous system, but, the consequences of its loss on cell physiology are still rather obscure. The comprehension of the cellular mechanisms affected by the loss of MeCP2 is crucial to understand the disease and for the design of appropriate pharmacology. The mechanicistic study of this disease is complicated by the fact that in patients the brain presents a mosaic of healthy cells interspersed within diseased ones. This characteristic is common to other X-linked diseases and offers a difficult problem to be solved: if one desires to study the effects of the loss of MeCP2 at the level of a single cell, how is can be replicated the formation of this mosaic in a way in which it is possible to recognize healthy and diseased cells? The central idea of this project is the creation of a novel model of RS that answers to three crucial issues: 1) diseased and normal cells must be distributed in a mosaic; 2) the loss of MeCP2 can be directed to a specific cell type; 3) it must be possible to identify the cells that have lost MeCP2. In this model we will study the functions of control and of MeCP2 depleted cells placed in an ecosystem similar to the one present in patients. We will study how the loss of MeCP2 influences synaptic transmission and plasticity, the structure of dendrites and the interactions between neurons and supporting astrocytes.
PROJECT DETAILS
beginning: 2013.
end: 2016.
Country of research: Italy
Counry of funding source: Italy
Funding organization: Telethon
Financing: PRIVATE FUNDERS – 537 900 €