Department of Biological Sciences, University of Memphis, Memphis, Tennessee, United States of America.
PLoS One. 2013;8(1):e53635. doi: 10.1371/journal.pone.0053635. Epub 2013 Jan 9.
DOC-2/DAB-2 interacting protein (Dab2IP) is a GTPase activating protein that binds to Disabled-1, a cytosolic adapter protein involved in Reelin signaling and brain development. Dab2IP regulates PI3K-AKT signaling and is associated with metastatic prostate cancer, abdominal aortic aneurysms and coronary heart disease. To date, the physiological function of Dab2IP in the nervous system, where it is highly expressed, is relatively unknown. In this study, we generated a mouse model with a targeted disruption of Dab2IP using a retrovirus gene trap strategy. Unlike reeler mice, Dab2IP knock-down mice did not exhibit severe ataxia or cerebellar hypoplasia. However, Dab2IP deficiency produced a number of cerebellar abnormalities such as a delay in the development of Purkinje cell (PC) dendrites, a decrease in the parallel fiber synaptic marker VGluT1, and an increase in the climbing fiber synaptic marker VGluT2. These findings demonstrate for the first time that Dab2IP plays an important role in dendrite development and regulates the number of synapses in the cerebellum.
DOC-2/DAB-2 相互作用蛋白（Dab2IP）是一种 GTP 酶激活蛋白，与Disabled-1 结合，Disabled-1 是一种参与 Reelin 信号和大脑发育的细胞质衔接蛋白。Dab2IP 调节 PI3K-AKT 信号，与转移性前列腺癌、腹主动脉瘤和冠心病有关。迄今为止，Dab2IP 在神经系统中的生理功能（在神经系统中高度表达）相对未知。在这项研究中，我们使用逆转录病毒基因陷阱策略生成了一种靶向敲除 Dab2IP 的小鼠模型。与 reeler 小鼠不同，Dab2IP 敲除小鼠没有表现出严重的共济失调或小脑发育不良。然而，Dab2IP 缺失产生了许多小脑异常，例如浦肯野细胞（PC）树突发育延迟、平行纤维突触标记物 VGluT1 减少以及 climbing 纤维突触标记物 VGluT2 增加。这些发现首次表明 Dab2IP 在树突发育中发挥重要作用，并调节小脑的突触数量。
