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論文
- タイトル
- タイトル（英）
- The mouse model of intellectual disability by ZBTB18/RP58 haploinsufficiency shows cognitive dysfunction with synaptic impairment.
- 参照URL
- https://researchmap.jp/haruookado/published_papers/41326268
- 著者
- 著者（英）
- Sayaka Hirai,Hideki Miwa,Hiroko Shimbo,Keisuke Nakajima,Masahiro Kondo,Tomoko Tanaka,Chiaki Ohtaka-Maruyama,Shinobu Hirai,Haruo Okado
- 担当区分
- 概要
- 概要（英）
- ZBTB18/RP58 (OMIM *608433) is one of the pivotal genes responsible for 1q43q44 microdeletion syndrome (OMIM #612337) and its haploinsufficiency induces intellectual disability. However, the underlying pathological mechanism of ZBTB18/RP58 haploinsufficiency is unknown. In this study, we generated ZBTB18/RP58 heterozygous mice and found that these mutant mice exhibit multiple behavioral deficits, including impairment in motor learning, working memory, and memory flexibility, which are related to behaviors in people with intellectual disabilities, and show no gross abnormalities in their cytoarchitectures but dysplasia of the corpus callosum, which has been reported in certain population of patients with ZBTB18 haploinsufficiency as well as in those with 1q43q44 microdeletion syndrome, indicating that these mutant mice are a novel model of ZBTB18/RP58 haploinsufficiency, which reflects heterozygotic ZBTB18 missense, truncating variants and some phenotypes of 1q43q44 microdeletion syndrome based on ZBTB18/RP58 haploinsufficiency. Furthermore, these mice show glutamatergic synaptic dysfunctions, including a reduced glutamate receptor expression, altered properties of NMDA receptor-mediated synaptic responses, a decreased saturation level of long-term potentiation of excitatory synaptic transmission, and distinct morphological characteristics of the thick-type spines. Therefore, these results suggest that ZBTB18/RP58 haploinsufficiency leads to impaired excitatory synaptic maturation, which in turn results in cognitive dysfunction in ZBTB18 haploinsufficiency.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Molecular psychiatry
- 巻
- 号
- 開始ページ
- 終了ページ
- 出版年月
- 2023年2月1日
- 査読の有無
- 査読有り
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1038/s41380-023-01941-3
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