Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Laboratory of Children's Blood Diseases, Wuhan Children's Hospital, Huazhong University of Science and Technology, Wuhan, China.
Autism Res. 2023 Mar;16(3):524-534. doi: 10.1002/aur.2880. Epub 2022 Dec 19.
Tanc2 is a large multi-domain postsynaptic scaffold protein mainly expressed in the brain. In humans, tanc2 mutations have been associated with autism spectrum disorder (ASD) and other related neurodevelopmental disorders. However, the role of tanc2 in neurodevelopment and in controlling behaviors are not fully understood. Here, we generated and characterized a tanc2 knockout allele in zebrafish. Loss of tanc2 increases the larval brain size and body length by promoting proliferation and inhibiting apoptosis. We observed that the glutamatergic neuron population is significantly increased in tanc2 mutants while the GABAergic and the glycinergic neurons are not affected, suggesting that an excitatory/inhibitory (E/I) imbalance. Indeed, the tanc2 knockout 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 carrying tanc2 mutations. Therefore, the tanc2 knockout allele could serve as a valuable model to further study the role of tanc2 in the nervous system.
Tanc2 是一种大型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）和其他相关神经发育障碍有关。然而，tanc2 在神经发育和控制行为中的作用尚未完全阐明。在这里，我们在斑马鱼中生成并表征了一个 tanc2 敲除等位基因。tanc2 的缺失通过促进增殖和抑制凋亡，增加了幼虫的大脑大小和体长。我们观察到，在 tanc2 突变体中，谷氨酸能神经元群体显著增加，而 GABA 能和甘氨酸能神经元不受影响，提示兴奋性/抑制性（E/I）失衡。事实上，tanc2 敲除幼虫表现出睡眠增加。在成年斑马鱼中，突变体表现出焦虑样行为、攻击性降低和社交偏好受损。这些行为的改变与携带 tanc2 突变的 ASD 患者的表型相似。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。
