New Grant Supports Stem Cell-Derived Model of Autism-Related Illness

For the first time, researchers are developing a test tube model of Rett syndrome, a debilitating autism-like illness, in neurons derived from human embryonic stem cells. The study, recently funded by a grant from NIMH’s Division of Neuroscience and Basic Behavioral Science, addresses a crucial gap in understanding the workings of the rare autism spectrum disorder.

Rett syndrome strikes mostly girls when they are about a year old, triggering regression in language and thinking as well as impaired movement. It is caused by a deficiency in a gene called MECP2, which plays a pivotal role in turning other genes on and off in the developing brain, in response to experience. In fact, a recent NIH-supported study revealed that it serves as an “on” switch for about 2,200 genes and an “off” switch for about 400 genes in the mouse brain’s hypothalamus alone.

Yet, how mutations in the MECP2 gene cause the brain to malfunction remains unclear.

In what may be the most ambitious effort yet to find out, NIMH grantee Yi Eve Sun, Ph.D., of the University of California Los Angeles, is genetically-engineering neurons deficient in MECP2 from different NIH-approved human embryonic stem cell lines. She hopes to determine how gene expression might be altered in neurons deficient in MECP2, whether neurons lacking the gene can give birth to different subtypes of neurons, and how its absence may alter cell function.

The research will also determine how mutations in MECP2 may shift the balance between increased or decreased neuronal activity, whether MECP2 acts similarly in human and mouse neurons, and whether MECP2 mutations may render developing neurons more vulnerable to stressors.

“Our experiments will establish a model system for studying Rett syndrome in human neurons that might be helpful in the development of new medications  and therapeutic approaches,” said Sun.