Role of cerebellar Shank2 in the regulation of synaptic and behavioral functions = 소뇌의 Shank2 단백질이 시냅스 기능과 생쥐 행동에 미치는 영향 연구

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Shank2 is a multidomain scaffolding protein implicated in the structural and functional coordination of multiprotein complexes at excitatory postsynaptic sites as well as in psychiatric disorders, including autism spectrum disorders. While Shank2 is strongly expressed in the cerebellum, whether Shank2 regulates cerebellar excitatory synapses, or contributes to the behavioral abnormalities observed in $Shank2^{-/-}$ mice, remains unexplored. Here we show that $Shank2^{-/-}$ mice show reduced excitatory synapse density in cerebellar Purkinje cells in association with reduced levels of excitatory postsynaptic proteins including GluD2 and PSD-93 and impaired motor coordination in the Erasmus test. Shank2 deletion restricted to Purkinje cells ($Pcp2-Cre; Shank2^{fl/fl}$ mice) leads to similar reductions in excitatory synapse density, synaptic protein levels, and motor coordination. $Pcp2-Cre; Shank2^{fl/fl}$ mice do not recapitulate autistic-like behaviors observed in $Shank2^{-/-}$ mice, such as social-interaction deficits, altered ultrasonic vocalizations, repetitive behaviors, and hyperactivity. However, $Pcp2-Cre; Shank2^{fl/fl}$ mice display enhanced repetitive behavior in the hole-board test and anxiety-like behavior in the light-dark test, which are not observed in $Shank2^{-/-}$ mice. These results implicate Shank2 in the regulation of cerebellar excitatory synapse density, motor coordination, and specific repetitive and anxiety-like behaviors.
Advisors
Kim, Eunjoonresearcher김은준researcher
Description
한국과학기술원 :생명과학과,
Publisher
한국과학기술원
Issue Date
2018
Identifier
325007
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생명과학과, 2018.2,[ii, 94 p. :]

Keywords

autism▼acerebellum▼aexcitatory synapse▼aPurkinje cell▼aShank2; 자폐▼a소뇌▼a흥분성 시냅스▼a퍼킨지 세포▼aShank2

URI
http://hdl.handle.net/10203/264767
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=734323&flag=dissertation
Appears in Collection
BS-Theses_Ph.D.(박사논문)
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