Researchers at Baylor College of Medicine and the Jan and Dan Duncan Neurological Research Institute have uncovered molecular changes linked to Rett syndrome. This severe neurological disorder is caused by mutations in the MeCP2 gene, which encodes the methyl-CpG binding protein 2 (MeCP2). The study, published in Neuron, reveals that losing MeCP2 in adulthood leads to dysregulation of hundreds of genes before any noticeable neurological deficiencies.
The MeCP2 protein is predominantly found in neurons and regulates gene expression necessary for normal brain function. "In the current study, our goal was to better understand the molecular changes that occur upon loss of MeCP2 function," said Dr. Sameer S. Bajikar, first author of the study.
The research team focused on adult life to identify gene dysregulation due to MeCP2 loss. "We conditionally deleted Mecp2 in adult mice," explained Bajikar. This approach revealed early gene expression changes independent of developmental contributions.
Key findings showed that genes with persistent dysregulation were highly tagged with methyl groups affecting neuronal function. Dr. Huda Zoghbi highlighted a critical window where molecular events occur before physiological consequences are evident: "Our data demonstrate that there is a window of time when molecular events downstream of MeCP2 are occurring."
Contributors to this research include Jian Zhou, Ryan O’Hara, Harini P. Tirumala, among others from various institutions like Baylor College of Medicine and UT Southwestern Medical Center.
This work received support from several grants including those from the Eunice Kennedy Shriver National Institute of Child Health and Development and Howard Hughes Medical Institute.
