Jacobsen syndrome is a rare genetic disorder in which a child is born missing a portion of one copy of chromosome 11. This gene loss leads to multiple clinical challenges, such as congenital heart disease, intellectual disability, developmental and behavioral problems, slow growth and failure to thrive.

Researchers developed a mouse model of the Jacobsen syndrome that also exhibits autism-like social behaviors and used it to unravel the molecular mechanism that connects the genetic defects inherited in Jacobsen syndrome to effects on brain function.

The study, published in Nature Communications, also demonstrates that the anti-anxiety drug clonazepam reduces autistic features in the Jacobsen syndrome mice.

Previous research suggested that PX-RICS might be the missing chromosome 11 gene that leads to autism in children with Jacobsen syndrome. To investigate further, researchers who had already been studying PX-RICS for its role in brain development, but were unaware of the link to autism in humans.

In this study, the researchers determined that PX-RICS is most likely the gene responsible for autism-like symptoms in Jacobsen syndrome. To do this, they performed several well-established tests that measure common autism symptoms -- anti-social behavior, repetitive activities and inflexible adherence to routines.

As compared to normal mice, mice lacking PX-RICS spent less time on social activities (e.g., nose-to-nose sniffing and huddling) and were more apathetic or avoidant when approached by a stimulator mouse. PX-RICS-deficient mice also spent more than twice as much time on repetitive behaviors such as self-grooming and digging than normal mice. In addition, mice lacking PX-RICS more closely adhered to a previously established habit and were less able to adapt their behavior in novel situations.

Authros explored the molecular mechanism connecting lack of PX-RICS to behavior. They found that mice lacking the PX-RICS gene were also deficient in GABA_AR, a protein crucial for normal neuron function. That observation inspired the researchers to test clonazepam, a commonly used anti-anxiety drug that works by boosting GABA_AR, as a potential treatment for autism-like symptoms in these Jacobsen syndrome mice.

PX-RICS-deficient mice treated with low, non-sedating doses of clonazepam behaved almost normally in social tests, experienced improvements in learning performance and were better able to deviate from established habits.

http://ucsdnews.ucsd.edu/pressrelease/mouse_model_yields_possible_treatment_for_autism_like_symptoms_in_rare_dise