RETRACTED: Enhanced Polyubiquitination of Shank3 and NMDA Receptor in a Mouse Model of Autism | Zendy

Muhammad Bangash | Zendy; Joo Min Park | Zendy; Tatiana Melnikova | Zendy; Dehua Wang | Zendy; Soo Kyeong Jeon | Zendy; Deidre Lee | Zendy; Sbaa Syeda | Zendy; Juno Kim | Zendy; Mehreen Kouser | Zendy; Joshua L. Schwartz | Zendy; Yiyuan Cui | Zendy; Xia Zhao | Zendy; Haley E. Speed | Zendy; Sara E. Kee | Zendy; Jian Cheng Tu | Zendy; Jiahua Hu | Zendy; Ronald S. Petralia | Zendy; David J. Linden | Zendy; Craig M. Powell | Zendy; Alena Savonenko | Zendy; Bo Xiao | Zendy; Paul F. Worley | Zendy

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RETRACTED: Enhanced Polyubiquitination of Shank3 and NMDA Receptor in a Mouse Model of Autism

Author(s) -

Muhammad Bangash,

Joo Min Park,

Tatiana Melnikova,

Dehua Wang,

Soo Kyeong Jeon,

Deidre Lee,

Sbaa Syeda,

Juno Kim,

Mehreen Kouser,

Joshua L. Schwartz,

Yiyuan Cui,

Xia Zhao,

Haley E. Speed,

Sara E. Kee,

Jian Cheng Tu,

Jiahua Hu,

Ronald S. Petralia,

David J. Linden,

Craig M. Powell,

Alena Savonenko,

Bo Xiao,

Paul F. Worley

Publication year - 2011

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2011.03.052

Subject(s) - biology , nmda receptor , haploinsufficiency , synapse , postsynaptic potential , microbiology and biotechnology , dendritic spine , ubiquitin , long term potentiation , mutation , phenotype , receptor , neuroscience , genetics , gene , hippocampal formation

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(+/ΔC) mice], Shank3ΔC 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(+/ΔC) 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(+/ΔC) 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.

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