Knockout of tanc2 causes autism-like behavior and sleep disturbance in zebrafish
Knockout of tanc2 causes autism-like behavior and sleep disturbance in zebrafish
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DOI：
10.1002/aur.2880
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发表时间：
2022-12-19
期刊：
影响因子：
4.7
通讯作者：
Xiong，Bo
中科院分区：
文献类型：
--
作者：
Long，Fei;Zheng，Jing;Xiong，Bo
tanc2是一个大的多结构域突触后支架蛋白，主要在大脑中表达。在人类中，tanc2突变与自闭症谱系障碍（ASD）和其他相关的神经发育障碍有关。然而，在神经发育和控制行为中的作用尚不完全清楚。在这里，我们在斑马鱼中产生并表征了atanc2敲除等位基因。tanc2的缺失通过促进增殖和抑制细胞凋亡而增加了幼虫的脑大小和体长。我们观察到，在2突变体中，谷氨酸能神经元数量显著增加，而gaba能和甘氨酸能神经元未受影响，这表明存在兴奋性/抑制性（E/I）失衡。事实上，敲除tanc2的幼虫睡眠增加。在成年斑马鱼中，突变体表现出焦虑行为、攻击性降低和社会偏好受损。这些行为的改变在表型上与携带tanc2突变的ASD患者相似。因此，tanc2敲除等位基因可以作为一个有价值的模型，进一步研究tanc2在神经系统中的作用。
Tanc2is a large multi‐domain postsynaptic scaffold protein mainly expressed in the brain. In humans,tanc2mutations have been associated with autism spectrum disorder (ASD) and other related neurodevelopmental disorders. However, the role oftanc2in neurodevelopment and in controlling behaviors are not fully understood. Here, we generated and characterized atanc2knockout allele in zebrafish. Loss oftanc2increases the larval brain size and body length by promoting proliferation and inhibiting apoptosis. We observed that the glutamatergic neuron population is significantly increased intanc2mutants while the GABAergic and the glycinergic neurons are not affected, suggesting that an excitatory/inhibitory (E/I) imbalance. Indeed, thetanc2knockout larvae exhibited increase sleep. In adult zebrafish, the mutants display anxiolytic‐behavior, reduced aggression, and impaired social preference. The alterations in these behaviors are phenotypically similar to the ASD patients carryingtanc2mutations. Therefore, thetanc2knockout allele could serve as a valuable model to further study the role oftanc2in the nervous system.