Research Awardees: G.E.A.R.
     Abstracts

Michael Greenberg , Ph.D.

Children's Hospital Boston, Harvard
Develoment of Novel Antibody Reagents for MeCP2
$210,000

2005

Juan Botas, Ph.D.
Baylor College of Medicine
Genetic approaches to identify compensatory mechanisms preventing or ameliorating Rett Syndrome pathogenesis
$361,020
Research Sponsor: Gordon and Anne Rich/Reading Rock, Inc.

Lay Progress Report (August 2006)
Rett syndrome is a devastating neurological disorder affecting ~1 in 15,000 girls and leading to developmental regression and mental retardation. Most cases of Rett syndrome are caused by mutations in a gene called MeCP2. This gene works by preventing other "target" genes from functioning in the wrong time and place. Therefore, improper control of genes in the brain caused by MECP2 mutations is thought to cause Rett Syndrome. One possible avenue for therapy is to identify the MeCP2 target genes wrongly functioning during disease and to restore their normal control. An alternative approach is to identify molecular mechanisms capable of compensating for the improper control of target genes caused by MeCP2 mutations.

We are utilizing the fruit fly Drosophila as a novel in vivo system to identify components of the molecular machinery that functions antagonistically to MeCP2 and to alter its activity to compensate for MeCP2 loss of function. With this objective in mind, we generated transgenic Drosophila strains expressing human MECP2. We have already identified genetic modifiers in these animals expressing MeCP2 and we believe that they will lead to the identification of factors that are capable of compensating for MeCP2 lack of function. We will use mammalian cell systems to validate our findings in Drosophila, and to define possible therapeutic approaches.