Removing SAPAP3 caused compulsive grooming and anxiety behaviors, while reinserting it prevented these symptoms.
Researchers say that they were able to create a set of behaviors similar to obsessive-compulsive disorder (OCD) in mice and reversed them with reinsertion of the gene SAPAP3.
The team, led by sceintists at Duke University, weren’t initially interested in OCD. They sought to understand the function of the protein made by the SAPAP3 gene, which is involved in glutamate-mediated communications in the cortex-striatum circuit.
They found that SAPAP3 knockout mice were normal at first, but after four to six months, they developed bald patches of raw flesh on their faces, caused by compulsive scratching. These mice also showed anxiety-like behaviors. They were slower to venture into and quicker to exit risky environments. Also, like OCD people, the animals responded positively to treatment with a serotonin selective reuptake inhibitor.
The scientists also discovered that lack of SAPAP3 gene dampened the increased activity usually caused by glutamate and stunted the development and functioning of circuit connections.
When the researchers injected the striatum of seven-day old knockout mice with a probe containing the SAPAP3 gene, it protected them from developing the OCD and anxiety-like symptoms and corrected the circuit dysfunction.
The study will be publsihed in the August 23 issue of Nature.