| First Author | Portmann T | Year | 2014 |
| Journal | Cell Rep | Volume | 7 |
| Issue | 4 | Pages | 1077-1092 |
| PubMed ID | 24794428 | Mgi Jnum | J:210018 |
| Mgi Id | MGI:5569355 | Doi | 10.1016/j.celrep.2014.03.036 |
| Citation | Portmann T, et al. (2014) Behavioral abnormalities and circuit defects in the Basal Ganglia of a mouse model of 16p11.2 deletion syndrome. Cell Rep 7(4):1077-92 |
| abstractText | A deletion on human chromosome 16p11.2 is associated with autism spectrum disorders. We deleted the syntenic region on mouse chromosome 7F3. MRI and high-throughput single-cell transcriptomics revealed anatomical and cellular abnormalities, particularly in cortex and striatum of juvenile mutant mice (16p11(+/-)). We found elevated numbers of striatal medium spiny neurons (MSNs) expressing the dopamine D2 receptor (Drd2(+)) and fewer dopamine-sensitive (Drd1(+)) neurons in deep layers of cortex. Electrophysiological recordings of Drd2(+) MSN revealed synaptic defects, suggesting abnormal basal ganglia circuitry function in 16p11(+/-) mice. This is further supported by behavioral experiments showing hyperactivity, circling, and deficits in movement control. Strikingly, 16p11(+/-) mice showed a complete lack of habituation reminiscent of what is observed in some autistic individuals. Our findings unveil a fundamental role of genes affected by the 16p11.2 deletion in establishing the basal ganglia circuitry and provide insights in the pathophysiology of autism. |
