This project addresses the complex relationship between the development of Rett Syndrome (RTT), and the normal function of the protein involved, Methyl-CpG Binding Protein 2 (MeCP2). RTT is a devastating neurological disorder showing first symptoms around the age of 6-12 months in the form of delayed motor skills and social withdrawal. Later, purposeful hand use is lost while stereotypic hand movements emerge and any obtained language is lost. The progression of RTT is perplexing because of this seemingly normal initial development and because of the loss of acquired speech. The gene involved in development of the disorder, MECP2, encodes a protein which has the ability of repressing transcription of certain genes. Through this project we wish to clarify the neuropathology of RTT in respect to normal function of MeCP2. With that aim, different RTT mouse models generated are studied. MeCP2 is important during maturation of neurons and for normal function of mature neurons. Genes that appear to be affected are involved in synapse- and dendrite development and mutated MECP2 results in reduced brain size, stunted neuronal connections, densely packed neurons, and diminished nuclei size. The symptoms of seizures and stereotypic hand movements are likely to be caused by elevated excitatory stimulation seen in young RTT patients. The decreased density of glutamate receptors that sets in around the age of eight years can explain the relative stabilization of phenotype around this time. The initial symptom of impaired locomotion is caused by disruption of serotonergic- and noradrenergic neurons in the brainstem. Further investigation is needed to clarify the cause of the distinct RTT symptoms and to understand the progression of disease.
|Uddannelser||Molekylærbiologi, (Bachelor/kandidatuddannelse) Bachelor el. kandidat|
|Udgivelsesdato||29 jan. 2009|
- Phenotype geneotype correlation
- Rett syndrome
- brain dysfunction
- Transcriptional repressor