Research Awards
Janine LaSalle, Ph.D.
University of California at Davis
"The Role of MeCP2 in the Ontogeny of Cerebral Cortical Neurons"
1-Year Award: $50,000
Research Sponsor: Reading Rock Inc.
Lay Progress Report (August, 2004)
Rett syndrome is cause by mutations in the gene MECP2 that encodes a protein, methyl-CpG protein 2 (MeCP2). Elevated MeCP2 expression is acquired in individual neurons within the brain beginning in infancy and progressing throughout childhood. The function of MeCP2 in the developing brain is unclear at this stage, but the mutations in Rett syndrome and the Mecp2 "knockout" mouse model provide evidence that MeCP2 is essential for mature neuronal function. MeCP2 is predicted to be a regulator of other genes in maturing neurons, but finding these genes is complicated by the complexity of cells and genes in the brain. The first aim of this proposal was to use a cell culture system for inducing neuronal maturation to identify genes expressed in a single cell type at a precise time. MeCP2 activity was blocked by using a "decoy" inserted into the cells. Genes that show significantly altered expression levels in cells with blocked MeCP2 activity were identified by "gene chip" technology. In the second aim of this proposal, candidate genes identified in Aim 1 will be tested for expression patterns in normal and MECP2/Mecp2 mutant human and mouse brain samples. An automated approach of quantitating proteins in multiple tissue samples by laser scanning cytometry has recently been developed by the PI and will be used to test the effect of MECP2/Mecp2 mutations on the normal developmental expression of the candidate genes. The results from these studies are expected to provide new information for understanding how MECP2 mutations cause Rett syndrome and provide multiple novel molecules that could be targeted for therapeutic intervention.
Janine LaSalle, Ph.D.University of California at Davis
"The Role of MeCP2 in the Ontogeny of Cerebral Cortical Neurons"
1-Year Award: $50,000
Research Sponsor: Reading Rock Inc.
Lay Progress Report (August, 2004)
Rett syndrome is cause by mutations in the gene MECP2 that encodes a protein, methyl-CpG protein 2 (MeCP2). Elevated MeCP2 expression is acquired in individual neurons within the brain beginning in infancy and progressing throughout childhood. The function of MeCP2 in the developing brain is unclear at this stage, but the mutations in Rett syndrome and the Mecp2 "knockout" mouse model provide evidence that MeCP2 is essential for mature neuronal function. MeCP2 is predicted to be a regulator of other genes in maturing neurons, but finding these genes is complicated by the complexity of cells and genes in the brain. The first aim of this proposal was to use a cell culture system for inducing neuronal maturation to identify genes expressed in a single cell type at a precise time. MeCP2 activity was blocked by using a "decoy" inserted into the cells. Genes that show significantly altered expression levels in cells with blocked MeCP2 activity were identified by "gene chip" technology. In the second aim of this proposal, candidate genes identified in Aim 1 will be tested for expression patterns in normal and MECP2/Mecp2 mutant human and mouse brain samples. An automated approach of quantitating proteins in multiple tissue samples by laser scanning cytometry has recently been developed by the PI and will be used to test the effect of MECP2/Mecp2 mutations on the normal developmental expression of the candidate genes. The results from these studies are expected to provide new information for understanding how MECP2 mutations cause Rett syndrome and provide multiple novel molecules that could be targeted for therapeutic intervention.