Post Doctoral Fellowships
Peng Jin, Ph.D.
Emory University School of Medicine
Mentor: Stephen Warren, Ph.D.
"Identification of Target Genes of MeCP2 in Neurons"
2-Year Award: $100,000
Final Report (November 2004)
Rett Syndrome is a neurodevelopmental disorder mainly caused by mutations in the X-linked gene MECP2 and primarily affects females. MeCP2 binds to methylated DNA and blocks gene expression. Mutations in MeCP2 affect its ability to block gene expression and may lead to aberrant patterns of gene expression in RTT. The predominant manifestation of central nervous system dysfunction in RTT suggests that MeCP2 plays a critical role in the development and stability of neurons. However, the downstream target genes regulated by MeCP2 in neurons have not been identified, which will be important for the development of therapeutic approaches. In this study we proposed to use RTT mouse model to identify these target genes. Using RTT mouse model and advanced cell sorting technology, we have isolated specific neurons, Purkinje cells, to study the change of gene expression pattern in the absence of MeCP2 using DNA microarray analysis. Our results suggest that a group of genes involved in protein synthesis were altered in the absence of MeCP2 at day seven, a critical stage for brain development. This indicates that defects in protein synthesis may associate with Rett Syndrome and be responsible for its neurological phenotype.
Peng Jin, Ph.D.Emory University School of Medicine
Mentor: Stephen Warren, Ph.D.
"Identification of Target Genes of MeCP2 in Neurons"
2-Year Award: $100,000
Final Report (November 2004)
Rett Syndrome is a neurodevelopmental disorder mainly caused by mutations in the X-linked gene MECP2 and primarily affects females. MeCP2 binds to methylated DNA and blocks gene expression. Mutations in MeCP2 affect its ability to block gene expression and may lead to aberrant patterns of gene expression in RTT. The predominant manifestation of central nervous system dysfunction in RTT suggests that MeCP2 plays a critical role in the development and stability of neurons. However, the downstream target genes regulated by MeCP2 in neurons have not been identified, which will be important for the development of therapeutic approaches. In this study we proposed to use RTT mouse model to identify these target genes. Using RTT mouse model and advanced cell sorting technology, we have isolated specific neurons, Purkinje cells, to study the change of gene expression pattern in the absence of MeCP2 using DNA microarray analysis. Our results suggest that a group of genes involved in protein synthesis were altered in the absence of MeCP2 at day seven, a critical stage for brain development. This indicates that defects in protein synthesis may associate with Rett Syndrome and be responsible for its neurological phenotype.