Autism-associated Dyrk1a truncation mutants impair neuronal dendritic and spine growth and interfere with postnatal cortical development

被引：50
作者：
Dang, T. [1 ,2 ]
Duan, W. Y. [3 ,7 ]
Yu, B. [4 ]
Tong, D. L. [4 ]
Cheng, C. [4 ]
Zhang, Y. F. [4 ]
Wu, W. [3 ,8 ]
Ye, K. [3 ,9 ]
Zhang, W. X. [3 ,10 ]
Wu, M. [1 ,2 ,3 ]
Wu, B. B. [1 ,2 ,3 ]
An, Y. [1 ,2 ,3 ]
Qiu, Z. L. [4 ]
Wu, B. L. [1 ,2 ,5 ,6 ]
机构：
[1] Fudan Univ, Childrens Hosp, Shanghai, Peoples R China
[2] Fudan Univ, Inst Biomed Sci, Shanghai Med Coll, Shanghai, Peoples R China
[3] Fudan Univ, Shanghai Med Coll, Exome Sequencing Collaborat Boston Childrens Hosp, Shanghai, Peoples R China
[4] Chinese Acad Sci, CAS Key Lab Primate Neurobiol, CAS Ctr Excellence Brain Sci & Intelligence Techn, Inst Neurosci,Shanghai Inst Biol Sci,State Key La, Shanghai, Peoples R China
[5] Boston Childrens Hosp, Boston, MA 02115 USA
[6] Harvard Med Sch, Boston, MA 02115 USA
[7] Gen Hosp Jinan Mil Reg, Inst Cardiovasc Dis, 8 Lashan Rd, Jinan 250022, Shandong, Peoples R China
[8] Nanjing Med Univ, Affiliated Hosp 1, State Key Lab Reprod Med, Ctr Reprod Med, 300 Guangzhou Rd, Nanjing 210029, Jiangsu, Peoples R China
[9] Suzhou Municipal Hosp, Child Hlth Care Dept, 26 Daoqian St, Suzhou 215002, Jiangsu, Peoples R China
[10] Anhui Med Univ, PLA, Hosp 105, Reprod Med Ctr, Hefei 230031, Anhui, Peoples R China
来源：
MOLECULAR PSYCHIATRY | 2018年 / 23卷 / 03期
关键词：
2 UNRELATED PATIENTS; DOWN-SYNDROME; INTELLECTUAL DISABILITY; SPECTRUM DISORDERS; CELL-PROLIFERATION; TS65DN MICE; ALZHEIMER-DISEASE; DENTATE GYRUS; MOUSE MODEL; PHOSPHORYLATION;
D O I：
10.1038/mp.2016.253
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Autism is a prevailing neurodevelopmental disorder with a large genetic/genomic component. Recently, the dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A) gene was implicated as a risk factor for autism spectrum disorder (ASD). We identified five DYRK1A variants in ASD patients and found that the dose of DYRK1A protein has a crucial role in various aspects of postnatal neural development. Dyrk1a loss of function and gain of function led to defects in dendritic growth, dendritic spine development and radial migration during cortical development. Importantly, two autism-associated truncations, R205X and E239X, were shown to be Dyrk1a loss-of-function mutants. Studies of the truncated Dyrk1a mutants may provide new insights into the role of Dyrk1a in brain development, as well as the role of Dyrk1a loss of function in the pathophysiology of autism.
引用
收藏
页码：747 / 758
页数：12
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