한빛사논문
- 조회444
Seongbin Kim,1,9 Hyoseon Oh,1,9 Sang Han Choi,2,3 Ye-Eun Yoo,4 Young Woo Noh,1 Yisul Cho,5 Geun Ho Im,2 Chanhee Lee,2 Yusang Oh,6 Esther Yang,7 Gyuri Kim,1 Won-Suk Chung,1 Hyun Kim,7 Hyojin Kang,8 Yongchul Bae,5 Seong-Gi Kim,2,3 and Eunjoon Kim1,4,10,*
1Department of Biological Sciences, Korea Advanced Institute for Science and Technology (KAIST), Daejeon 34141, Korea
2Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon 16419, Korea
3Department of Biomedical Engineering, Sungkyunkwan University, Suwon 16419, Korea
4Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon 34141, Korea
5Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu 41940, Korea
6Department of Bio and Brain Engineering, Korea Advanced Institute for Science and Technology (KAIST), Daejeon 34141, Korea
7Department of Anatomy and BK21 Graduate Program, Biomedical Sciences, College of Medicine, Korea University, Seoul 02841, Korea
8Division of National Supercomputing, Korea Institute of Science and Technology Information (KISTI), Daejeon 34141, Korea
9These authors contributed equally
10Lead contact
*Correspondence
Abstract
Myelin transcription factor 1 like (Myt1l), a zinc-finger transcription factor, promotes neuronal differentiation and is implicated in autism spectrum disorder (ASD) and intellectual disability. However, it remains unclear whether Myt1l promotes neuronal differentiation in vivo and its deficiency in mice leads to disease-related phenotypes. Here, we report that Myt1l-heterozygous mutant (Myt1l-HT) mice display postnatal age-differential ASD-related phenotypes: newborn Myt1l-HT mice, with strong Myt1l expression, show ASD-like transcriptomic changes involving decreased synaptic gene expression and prefrontal excitatory synaptic transmission and altered righting reflex. Juvenile Myt1l-HT mice, with markedly decreased Myt1l expression, display reverse ASD-like transcriptomes, increased prefrontal excitatory transmission, and largely normal behaviors. Adult Myt1l-HT mice show ASD-like transcriptomes involving astrocytic and microglial gene upregulation, increased prefrontal inhibitory transmission, and behavioral deficits. Therefore, Myt1l haploinsufficiency leads to ASD-related phenotypes in newborn mice, which are temporarily normalized in juveniles but re-appear in adults, pointing to continuing phenotypic changes long after a marked decrease of Myt1l expression in juveniles.
논문정보
- Research article
- 2022년 09월 (BRIC 등록일 2022-09-29)
- 국내 연구진
- 생명과학 > 생리학
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