Our work on Rett Syndrome
Although the discovery of MeCP2 mutations in more than 90% of Rett syndrome cases was a very important step to understand the molecular basis of the disease, it did not allow to understand its pathophysiology. However, the identification of the MeCP2 gene lead to the creation of an animal model of the disease : transgenic mice with a deletion of the Mecp2 gene (Guy et al., 2001). These animals quite nicely reproduce the natural history and the clinical signs of Rett syndrome. It is an extremely useful tool to address the questions of how this disease occurs and what are the molecular and cellular mechanisms at play.
We study the brainstem of the mouse model for Rett syndrome. Why ? Because a number of clinical signs observed in Rett syndrome patients could be due to a dysfunction of the brainstem. This portion of the nervous system is responsible, among other things, for the generation of proper breathing and cardiac rhythms. To study this structure thus seems particularly relevant because up to 30% of Rett syndrome patients could decease of sudden death, likely following a cardio-respiratory failure. We use magnetic resonance imaging and transcriptional analysis to reveal the consequences of Mecp2 dysfunction. We are also strongly involved in therapeutic development using the "Rett" mouse as a pre-clinical model.
Our research is developped along the following axis :
1- study of autonomic dysfunction, description of the cellular and molecular defects present in the animal model.
To learn more about this project, follow this link >AUTONOMIC DYSFUNCTION<.
2- transcriptional profiling of the brainstem of mutant animals using the technology of "DNA microarrays" followed by a validation of the results using real-time PCR and immunohistochemistry.
To learn more about this project, follow this link >TRANSCRIPTIONAL PROFILING<.
3- can we use these results to design new pharmacological interventions or understand RS pathophysiology ?
To learn more about this project, follow this link >THERAPEUTIC APPROACHES<.
4- In addition, to gain further informations about these "Rett" mice, we have designed a new research program using in vivo magnetic resonance imaging (MRI) with Dr. Angèle Viola in Prof. Patrick Cozzone's laboratory which is located in the same institute and is one of the best laboratories to investigate biochemical and structural features in model animals using MRI. This program already generated its first results.
To learn more about this project, follow this link >MAGNETIC RESONANCE IMAGING<.
5- In 2008, a new research network on Rett syndrome was created. This network is called EuroRETT and regroups 10 laboratories in 5 countries.
To know more about the network, follow this link >RESEARCH NETWORK<.