Other
11 Authors
- Dietz DM,
- Qin L,
- Duffney LJ,
- Yan Z,
- Ma K,
- Wei J,
- Cheng J,
- Buxbaum JD,
- Zhong P,
- Kajiwara Y,
- Matas E
| First Author | Duffney LJ | Year | 2015 |
| Journal | Cell Rep | Volume | 11 |
| Issue | 9 | Pages | 1400-1413 |
| PubMed ID | 26027926 | Mgi Jnum | J:228584 |
| Mgi Id | MGI:5707990 | Doi | 10.1016/j.celrep.2015.04.064 |
| Citation | Duffney LJ, et al. (2015) Autism-like Deficits in Shank3-Deficient Mice Are Rescued by Targeting Actin Regulators. Cell Rep 11(9):1400-13 |
| abstractText | Haploinsufficiency of the Shank3 gene, which encodes a scaffolding protein at glutamatergic synapses, is a highly prevalent and penetrant risk factor for autism. Using combined behavioral, electrophysiological, biochemical, imaging, and molecular approaches, we find that Shank3-deficient mice exhibit autism-like social deficits and repetitive behaviors, as well as the significantly diminished NMDA receptor (NMDAR) synaptic function and synaptic distribution in prefrontal cortex. Concomitantly, Shank3-deficient mice have a marked loss of cortical actin filaments, which is associated with the reduced Rac1/PAK activity and increased activity of cofilin, the major actin depolymerizing factor. The social deficits and NMDAR hypofunction are rescued by inhibiting cofilin or activating Rac1 in Shank3-deficient mice and are induced by inhibiting PAK or Rac1 in wild-type mice. These results indicate that the aberrant regulation of synaptic actin filaments and loss of synaptic NMDARs contribute to the manifestation of autism-like phenotypes. Thus, targeting actin regulators provides a strategy for autism treatment. |
