DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Kim, Eunjoon | - |
dc.contributor.advisor | 김은준 | - |
dc.contributor.author | Lee, Jiseok | - |
dc.contributor.author | 이지석 | - |
dc.date.accessioned | 2017-03-29T02:44:29Z | - |
dc.date.available | 2017-03-29T02:44:29Z | - |
dc.date.issued | 2016 | - |
dc.identifier.uri | http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=648152&flag=dissertation | en_US |
dc.identifier.uri | http://hdl.handle.net/10203/222090 | - |
dc.description | 학위논문(박사) - 한국과학기술원 : 생명과학과, 2016.2 ,[vi, 55 p. :] | - |
dc.description.abstract | Shank3 is a multi-domain scaffolding protein enriched in the postsynaptic density of excitatory synapses. By interacting with glutamate receptors and actin cytoskeleton regulatory proteins, Shank3 links excitatory neurotransmission with downstream signaling, thus functioning as a master organizer of postsynaptic sites. In humans, mutations in SHANK3 has been associated with autism spectrum disorder (ASD), a neurodevelopmental disorder characterized by impaired sociability and restricted, repetitive patterns of behavior. In this research, to establish an ASD animal model, I generated a knockout mouse line in which exon 9 of Shank3 was deleted $(Shank3^{Δ9 } mice)$. Among various Shank3 isoforms, $Shank3^{Δ9}$ mice specifically lacked isoforms containing the N-terminal ankyrin repeat region. These isoforms were enriched in the forebrain regions. In addition, I found that Shank3 isoforms show differential expression patterns in different brain regions. In $Shank3^{Δ9}$ mice, evoked excitatory transmission was suppressed in the hippocampus, and basal inhibitory but not excitatory transmission was altered differentially in the hippocampus and the medial prefrontal cortex. Behaviorally, $Shank3^{Δ9}$ mice did not show core autistic-like symptoms, but showed slightly increased rearing behavior in a novel environment, and mild deficits in spatial learning. These results suggest that ankyrin repeat-containing Shank3 isoforms are involved in regulating excitatory/inhibitory balance, and that deletion of these isoforms has subtle effects on specific behaviors. | - |
dc.language | eng | - |
dc.publisher | 한국과학기술원 | - |
dc.subject | Shank3 | - |
dc.subject | autism | - |
dc.subject | synaptic transmission | - |
dc.subject | excitatory/inhibitory (E/I) balance | - |
dc.subject | synaptic protein | - |
dc.subject | 자폐증 | - |
dc.subject | 시냅스 단백질 | - |
dc.subject | 시냅스 전달 | - |
dc.subject | 흥분성 시냅스 | - |
dc.subject | 억제성 시냅스 | - |
dc.title | Altered synaptic functions and behavior in autism-linked Shank3 knockout mice | - |
dc.title.alternative | 자폐증 연관 유전자 Shank3 결손 생쥐의 시냅스 기능과 행동 연구 | - |
dc.type | Thesis(Ph.D) | - |
dc.identifier.CNRN | 325007 | - |
dc.description.department | 한국과학기술원 :생명과학과, | - |
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