Research Awards
Laura Carrel, Ph.D.
Case Western Reserve University
"Expression Profile of the Inactive X Chromosome in Rett Syndrome: Role of MeCP2 in the establishment and maintenance of X inactivation."
2-Year Award: $95,790
Research Sponsor: Family & Friends of Jessie Lebson
Final Report:
Because the methyl-binding protein MeCP2 plays a role in regulating gene expression, Rett Syndrome is likely caused by misregulation of genes normally silenced by MeCP2. To date, the identity of such genes remains unknown. As methylation is involved normally in silencing genes on the inactive X chromosome, it is plausible that genes on the X are regulated by MeCP2 and therefore may be inappropriately expressed in cell lines from Rett syndrome patients. To test this hypothesis, we isolated the cell lines necessary for these experiments and assayed a number of X-linked genes. For all genes tested, reactivation was not observed in the Rett cell lines. Additionally, we looked for methylation changes at four X-linked genes, but also saw no significant differences between cell lines derived from Rett Syndrome individuals and normal controls. These studies argue that MeCP2 is either not involved in silencing the genes tested, or at a minimum, that it does not play an essential role in silencing these genes, at least in the cell lines examined. Assays have been developed that can be used to test additional genes on the X. While these studies could identify candidate genes that may be responsible for clinical features of Rett Syndrome, they may also help us to determine whether MeCP2 plays a role in silencing X-linked genes. However, as minimal changes have been observed in the cell lines examined, it may be more important to focus future studies on examining X-linked gene expression in the neuronal tissues that are affected in Rett Syndrome individuals by using the animal models that have been developed.
Laura Carrel, Ph.D.Case Western Reserve University
"Expression Profile of the Inactive X Chromosome in Rett Syndrome: Role of MeCP2 in the establishment and maintenance of X inactivation."
2-Year Award: $95,790
Research Sponsor: Family & Friends of Jessie Lebson
Final Report:
Because the methyl-binding protein MeCP2 plays a role in regulating gene expression, Rett Syndrome is likely caused by misregulation of genes normally silenced by MeCP2. To date, the identity of such genes remains unknown. As methylation is involved normally in silencing genes on the inactive X chromosome, it is plausible that genes on the X are regulated by MeCP2 and therefore may be inappropriately expressed in cell lines from Rett syndrome patients. To test this hypothesis, we isolated the cell lines necessary for these experiments and assayed a number of X-linked genes. For all genes tested, reactivation was not observed in the Rett cell lines. Additionally, we looked for methylation changes at four X-linked genes, but also saw no significant differences between cell lines derived from Rett Syndrome individuals and normal controls. These studies argue that MeCP2 is either not involved in silencing the genes tested, or at a minimum, that it does not play an essential role in silencing these genes, at least in the cell lines examined. Assays have been developed that can be used to test additional genes on the X. While these studies could identify candidate genes that may be responsible for clinical features of Rett Syndrome, they may also help us to determine whether MeCP2 plays a role in silencing X-linked genes. However, as minimal changes have been observed in the cell lines examined, it may be more important to focus future studies on examining X-linked gene expression in the neuronal tissues that are affected in Rett Syndrome individuals by using the animal models that have been developed.