Other
22 Authors
- Powell CM,
- Worley PF,
- Schwartz J,
- Tu JC,
- Wang D,
- Jeon SK,
- Hu JH,
- Cui Y,
- Petralia RS,
- Lee D,
- Linden DJ,
- Kim J,
- Park JM,
- Melnikova T,
- Kee SE,
- Savonenko A,
- Zhao X,
- Kouser M,
- Bangash MA,
- Speed HE,
- Xiao B,
- Syeda S
| First Author | Bangash MA | Year | 2011 |
| Journal | Cell | Volume | 145 |
| Issue | 5 | Pages | 758-72 |
| PubMed ID | 21565394 | Mgi Jnum | J:173397 |
| Mgi Id | MGI:5013992 | Doi | 10.1016/j.cell.2011.03.052 |
| Citation | Bangash MA, et al. (2011) Enhanced Polyubiquitination of Shank3 and NMDA Receptor in a Mouse Model of Autism. [RETRACTED Cell 2011 145(5) 758-72. Cell 145(5):758-72 |
| abstractText | We have created a mouse genetic model that mimics a human mutation of Shank3 that deletes the C terminus and is associated with autism. Expressed as a single copy [Shank3(+/DeltaC) mice], Shank3DeltaC protein interacts with the wild-type (WT) gene product and results in >90% reduction of Shank3 at synapses. This 'gain-of-function' phenotype is linked to increased polyubiquitination of WT Shank3 and its redistribution into proteasomes. Similarly, the NR1 subunit of the NMDA receptor is reduced at synapses with increased polyubiquitination. Assays of postsynaptic density proteins, spine morphology, and synapse number are unchanged in Shank3(+/DeltaC) mice, but the amplitude of NMDAR responses is reduced together with reduced NMDAR-dependent LTP and LTD. Reciprocally, mGluR-dependent LTD is markedly enhanced. Shank3(+/DeltaC) mice show behavioral deficits suggestive of autism and reduced NMDA receptor function. These studies reveal a mechanism distinct from haploinsufficiency by which mutations of Shank3 can evoke an autism-like disorder. |
