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Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function

DC FieldValueLanguage
dc.contributor.author이민구-
dc.contributor.author이정수-
dc.contributor.author정은석-
dc.contributor.author지헌영-
dc.date.accessioned2014-12-19T17:29:13Z-
dc.date.available2014-12-19T17:29:13Z-
dc.date.issued2012-
dc.identifier.issn0028-0836-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/91499-
dc.description.abstractAutism spectrum disorder (ASD) is a group of conditions characterized by impaired social interaction and communication, and restricted and repetitive behaviours. ASD is a highly heritable disorder involving various genetic determinants. Shank2 (also known as ProSAP1) is a multi-domain scaffolding protein and signalling adaptor enriched at excitatory neuronal synapses, and mutations in the human SHANK2 gene have recently been associated with ASD and intellectual disability. Although ASD-associated genes are being increasingly identified and studied using various approaches, including mouse genetics, further efforts are required to delineate important causal mechanisms with the potential for therapeutic application. Here we show that Shank2-mutant (Shank2(-/-)) mice carrying a mutation identical to the ASD-associated microdeletion in the human SHANK2 gene exhibit ASD-like behaviours including reduced social interaction, reduced social communication by ultrasonic vocalizations, and repetitive jumping. These mice show a marked decrease in NMDA (N-methyl-D-aspartate) glutamate receptor (NMDAR) function. Direct stimulation of NMDARs with D-cycloserine, a partial agonist of NMDARs, normalizes NMDAR function and improves social interaction in Shank2(-/-) mice. Furthermore, treatment of Shank2(-/-) mice with a positive allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), which enhances NMDAR function via mGluR5 activation, also normalizes NMDAR function and markedly enhances social interaction. These results suggest that reduced NMDAR function may contribute to the development of ASD-like phenotypes in Shank2(-/-) mice, and mGluR modulation of NMDARs offers a potential strategy to treat ASD.-
dc.description.statementOfResponsibilityopen-
dc.relation.isPartOfNature-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleAutistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Pharmacology (약리학)-
dc.contributor.googleauthorHyejung Won-
dc.contributor.googleauthorHye-Ryeon Lee-
dc.contributor.googleauthorHeon Yung Gee-
dc.contributor.googleauthorWon Mah-
dc.contributor.googleauthorJae-Ick Kim-
dc.contributor.googleauthorJiseok Lee-
dc.contributor.googleauthorSeungmin Ha-
dc.contributor.googleauthorChanguk Chung-
dc.contributor.googleauthorEun Suk Jung-
dc.contributor.googleauthorYi Sul Cho-
dc.contributor.googleauthorSae-Geun Park-
dc.contributor.googleauthorJung-Soo Lee-
dc.contributor.googleauthorKyungmin Lee-
dc.contributor.googleauthorDaesoo Kim-
dc.contributor.googleauthorYong Chul Bae-
dc.contributor.googleauthorBong-Kiun Kaang-
dc.contributor.googleauthorMin Goo Lee-
dc.contributor.googleauthorEunjoon Kim-
dc.identifier.doi10.1038/nature11208-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA03686-
dc.contributor.localIdA02781-
dc.contributor.localIdA03110-
dc.contributor.localIdA03971-
dc.relation.journalcodeJ02289-
dc.identifier.urlhttp://www.nature.com/nature/journal/v486/n7402/full/nature11208.html-
dc.contributor.alternativeNameLee, Min Goo-
dc.contributor.alternativeNameLee, Jung Soo-
dc.contributor.alternativeNameJung, Eun Suk-
dc.contributor.alternativeNameGee, Heon Yung-
dc.contributor.affiliatedAuthorJung, Eun Suk-
dc.contributor.affiliatedAuthorLee, Min Goo-
dc.contributor.affiliatedAuthorLee, Jung Soo-
dc.contributor.affiliatedAuthorGee, Heon Yung-
dc.citation.volume486-
dc.citation.number7402-
dc.citation.startPage261-
dc.citation.endPage265-
dc.identifier.bibliographicCitationNature, Vol.486(7402) : 261-265, 2012-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers

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