Reference:
Amendola, Elena
Abstract:
Rett syndrome is a neurodevelopmental disorder most commonly caused by mutations in the MECP2 gene. However, some persons with Rett do not carry mutations in MECP2 and recently mutations in the cyclin dependent kinase-like 5 (CDKL5) gene have been found in persons having a Rett-like disorder that includes seizures during the first six months of life. There are currently over 50 reported persons with such Rett-like disorders causes by mutations in CDKL5 and all children with CDKL5 mutations show similar features: seizures in the first months of life and subsequent development of Rett-like features. These observations indicate that CDKL5 might play a role in brain development similar to that of MECP2. They also suggest that a better understanding of the function of CDKL5 might help to better understand all forms of Rett. Interestingly, experiments in the laboratory have shown that CDKL5 can bind to and alter the function of MECP2 supporting the idea that they might act on similar brain functions to cause Rett. Nevertheless, little is known otherwise about the function of CDKL5 and a number of basic research tools are urgently needed to learn more about what this gene does in the brain and what goes wrong when it is mutated. Here we propose the development of several critical research tools and their use to address important questions about CDKL5 Rett. First, we plan to construct a mouse model of CDKL5 Rett; no mouse model of the disorder exists to date. Second, we will develop monoclonal antibodies, a renewable resource for distribution to Rett researchers that can be used to find out where CDKL5 functions in the brain. Third, we will perform experiments to find new molecules that help CDKL5 carry out its function and therefore might be defective in Rett. Together, these experiments aim to establish essential knowledge about the role of CDKL5 in brain development and will offer a platform for the testing of drugs to treat Rett. – See more at: http://www.rettsyndrome.org/research-programs/funded-projects/research-awardees-2010#sthash.Nk5rINCS.dpuf
PROJECT DETAILS
beginning: 2010.
end: 2012.
Country of research: Germany
Counry of funding source: United States
Funding organization: International Rett Syndrome Foundation (Postdoctoral Fellowship Grant)
Financing: PRIVATE FUNDERS – 146 872 €