At The Jackson Laboratory, we are committed to help find a treatment or cure for Rett syndrome. Our Rett syndrome mouse models are genetically stable, well characterized and critical tools in that endeavor. This article showcases some of the most promising of these mouse models and directs you to a few real-life stories of people who are working with our scientists to develop new models.
Rett syndrome is an autism spectrum disorder that almost exclusively affects girls, usually before they are two years old. Affected girls develop normally for the first 6-18 months but then lose speech and motor skills and may develop autistic behaviors, cognitive deficits, stereotyped hand movements (hand wringing), ataxia (abnormal gait), seizures, slow head growth (microcephaly) and cardiac and respiratory problems. Women with Rett syndrome can live well into adulthood; palliative care is key to their well-being.
The MECP2 gene and X-inactivation
Virtually all girls with Rett syndrome have a spontaneous mutation in the methyl-CpG binding protein 2 (MECP2) gene on the X chromosome. More than 200 mutations in eight different "hot spots" within the MECP2 locus have been associated with the disease. MECP2 is a widespread transcriptional regulator that binds to methylated DNA and blocks transcription. It is most concentrated in neurons of the brain and is highly expressed in the central nervous system during neuronal maturation. It may be involved in the alternative splicing of proteins critical for normal communication between nerve cells.
Although girls are born with two X chromosomes (one paternal and one maternal), in early embryonic development, in a process known as X-inactivation, one X chromosome is permanently inactivated. (Only one is needed to direct the production of enough MECP2 for cells to function normally.) Whether the chromosome with or without the mutant MECP2 allele is inactivated varies randomly from cell to cell. As a result, Rett syndrome ranges from mild to severe: the higher the percentage of cells whose active X chromosome has the mutant MECP2 allele, the more severe the disease.
We distribute numerous Rett syndrome mouse models, including the following:
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