Cognitive impairment and autistic-like behaviour in SAPAP4-deficient mice
Cognitive impairment and autistic-like behaviour in SAPAP4-deficient mice
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DOI：
10.1038/s41398-018-0327-z
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发表时间：
2019-01
影响因子：
6.8
通讯作者：
Claudia Schob;F. Morellini;Ora Ohana;L. Bakota;M. Hrynchak;R. Brandt;Marco D. Brockmann;Nicole Cichon;H. Hartung;I. Hanganu-Opatz;Vanessa Kraus;Sarah Scharf;Irm Herrmans-Borgmeyer;M. Schweizer;Dietmar Kuhl;M. Wöhr;K. J. Vörckel;J. Calzada-Wack;H. Fuchs;V. Gailus-Durner;M. Hrabě de Angelis;C. Garner;H. Kreienkamp;S. Kindler
中科院分区：
文献类型：
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作者：
Claudia Schob;F. Morellini;Ora Ohana;L. Bakota;M. Hrynchak;R. Brandt;Marco D. Brockmann;Nicole Cichon;H. Hartung;I. Hanganu-Opatz;Vanessa Kraus;Sarah Scharf;Irm Herrmans-Borgmeyer;M. Schweizer;Dietmar Kuhl;M. Wöhr;K. J. Vörckel;J. Calzada-Wack;H. Fuchs;V. Gailus-Durner;M. Hrabě de Angelis;C. Garner;H. Kreienkamp;S. Kindler
在人类中，DLGAP 1 - 4的遗传变异与神经精神疾病有关，包括自闭症谱系障碍（ASD）。虽然这些发现暗示编码的突触后蛋白SAPAP 1 -4在神经精神疾病的病因学中，但潜在的神经生物学机制尚不清楚。为了评估SAPAP 4对这些疾病的贡献，我们对SAPAP 4缺陷小鼠进行了表征。我们的研究表明，SAPAP 4的缺失引发了严重的行为异常，包括认知缺陷与受损的声音交流和社会互动，这些表型让人联想到人类的ASD。SAPAP 4缺陷小鼠的这些行为改变与突触形态、功能和可塑性的显著变化相关，表明SAPAP 4对于功能性神经元网络的发育至关重要，并且相应的人类基因DLGAP 4的突变可能导致与ASD样神经发育障碍相关的社会和认知功能的缺陷。
In humans, genetic variants ofDLGAP1-4have been linked with neuropsychiatric conditions, including autism spectrum disorder (ASD). While these findings implicate the encoded postsynaptic proteins, SAPAP1-4, in the etiology of neuropsychiatric conditions, underlying neurobiological mechanisms are unknown. To assess the contribution of SAPAP4 to these disorders, we characterized SAPAP4-deficient mice. Our study reveals that the loss of SAPAP4 triggers profound behavioural abnormalities, including cognitive deficits combined with impaired vocal communication and social interaction, phenotypes reminiscent of ASD in humans. These behavioural alterations of SAPAP4-deficient mice are associated with dramatic changes in synapse morphology, function and plasticity, indicating that SAPAP4 is critical for the development of functional neuronal networks and that mutations in the corresponding human gene,DLGAP4, may cause deficits in social and cognitive functioning relevant to ASD-like neurodevelopmental disorders.