Excess MeCP2 Protein Linked to Anxiety And Other Behavioral Issues

People with an excess of MeCP2 protein experience anxiety and a range of other behavioral issues, but Baylor College of Medicine scientists have just identified the particular genes involved, which they hope will lead to new treatments for those with too much of the protein. The full findings can be found in the journal Nature Genetics.

Among the many proteins synthesized by the body, MeCP2 is said to have a kind of "Goldilocks" effect. Too little can cause Rett syndrome in young girls, and too much can cause what has recently been labeled MeCP2 duplication syndrome in boys. It can be inherited from the mother or develop on its own. Aside from marked anxiety, MeCP2 duplication syndrome causes social, motor, and cognitive defects.

The findings come after a series of increasingly in-depth studies which began, of all places, in mice. The mouse model was used to identify human patients in a clinical setting, and, having identified the phenotype in humans, the researchers returned to the lab to pin down the exact genes responsible for its expression. Heightened MeCP2 levels cause altered expression of hundreds of genes, but the Crh (corticotropin-releasing hormone) and Oprm 1 (mu-opioid receptor MOR 1) were the two primarily responsible for observable symptoms.

In addition to merely identifying the genes, the Baylor group was able to adjust the expression of the Crh gene to make it less susceptible to the excess MeCP2, which is notoriously difficult to alter precisely. Beyond this particular gene-protein combination, this finding is important because it demonstrates very broadly the validity of—in certain cases—modifying the genes instead of the proteins.


Source: Baylor College of Medicine
Photo: Max Pixel

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