Homer1基因敲除小鼠模型在疾病研究中的应用

Homer1-KO (C57BL/6JCya-Homer1em1/Cya) Mouse Model

Homer1是一种突触后支架蛋白，具有多方面功能。它在谷氨酸能突触后密度（PSD）中整合不同的信号转导通路，调节运动和认知功能。此外，Homer1参与调控钙信号传导、I型代谢型谷氨酸受体的转运，并控制长时程增强和树突棘生长。

在与疾病相关的研究中，Homer1基因敲低和过表达的小鼠模型为科学界提供了重要见解。在脑出血（ICH）模型中，Homer1的过表达促进了A1型星形胶质细胞向A2型转化，抑制了MAPK信号通路，并改善了实验小鼠的恢复情况；而Homer1的敲低则产生了相反的效果。在大脑中动脉闭塞（MCAO）诱导的视网膜缺血模型中，Homer1的过表达通过抑制内质网应激相关的TXNIP/NLRP3炎性小体激活，保护了视网膜神经节细胞免于焦亡。在缺血性中风模型中，Homer1的敲低促进了神经元死亡和神经炎症，而注射Homer1蛋白则减少了坏死性凋亡引起的脑损伤。

综上所述，Homer1在多种生物学过程中发挥关键作用，特别是在脑出血、视网膜缺血和缺血性中风等条件下对炎症和细胞死亡的保护作用。Homer1基因敲除或敲低的小鼠模型已被证明是揭示其在这些疾病相关过程中的作用的重要工具，为相关疾病的潜在治疗靶点提供了方向。

参考文献：

1. Fei, Xiaowei, Dou, Ya-Nan, Wang, Li, Wei, Jialiang, Fei, Zhou. 2022. Homer1 promotes the conversion of A1 astrocytes to A2 astrocytes and improves the recovery of transgenic mice after intracerebral hemorrhage. In Journal of neuroinflammation, 19, 67. doi:10.1186/s12974-022-02428-8. https://pubmed.ncbi.nlm.nih.gov/35287697/
2. de Bartolomeis, Andrea, Barone, Annarita, Buonaguro, Elisabetta Filomena, Vellucci, Licia, Iasevoli, Felice. 2022. The Homer1 family of proteins at the crossroad of dopamine-glutamate signaling: An emerging molecular "Lego" in the pathophysiology of psychiatric disorders. A systematic review and translational insight. In Neuroscience and biobehavioral reviews, 136, 104596. doi:10.1016/j.neubiorev.2022.104596. https://pubmed.ncbi.nlm.nih.gov/35248676/
3. Lv, Weihao, Wu, Xiuquan, Dou, Yanan, Fei, Zhou, Fei, Fei. 2023. Homer1 Protects against Retinal Ganglion Cell Pyroptosis by Inhibiting Endoplasmic Reticulum Stress-Associated TXNIP/NLRP3 Inflammasome Activation after Middle Cerebral Artery Occlusion-Induced Retinal Ischemia. In International journal of molecular sciences, 24, . doi:10.3390/ijms242316811. https://pubmed.ncbi.nlm.nih.gov/38069134/
4. Lv, Weihao, Zhang, Qianqian, Li, Yuanming, Zhang, Lei, Fei, Zhou. 2023. Homer1 ameliorates ischemic stroke by inhibiting necroptosis-induced neuronal damage and neuroinflammation. In Inflammation research : official journal of the European Histamine Research Society ... [et al.], 73, 131-144. doi:10.1007/s00011-023-01824-x. https://pubmed.ncbi.nlm.nih.gov/38091015/

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