Neuronal abnormalities in microtubule-associated protein 1B mutant mice
Neuronal abnormalities in microtubule-associated protein 1B mutant mice
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DOI：
10.1073/pnas.93.3.1270
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发表时间：
1996-02-06
影响因子：
11.1
通讯作者：
Kucherlapati, R
中科院分区：
文献类型：
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作者：
Edelmann, W;Zervas, M;Kucherlapati, R
微管在建立细胞结构中起重要作用。神经元微管被认为在树突和轴突的形成中起作用，发育中和成年脑微管的不同部分与不同的微管相关蛋白（MAP）相关，不同MAP中的每一种的作用还不很清楚，这些蛋白中的一种，MAP 1B，在脑的不同部位表达，并被假定在神经元可塑性和脑发育中起作用。为了确定MAP 1B的作用，我们通过基因靶向方法产生了在该基因中携带插入物的小鼠。对于该修饰是纯合的小鼠在胚胎发生期间死亡。杂合子表现出一系列表型，包括生长速率较慢、单眼或双眼视力缺失和运动系统异常。对严重受累小鼠的组织化学分析显示，它们的浦肯野细胞树突状突起异常，不与MAP1B抗体反应，并且显示出与MAP1A抗体染色减少。在嗅球中观察到类似的组织学和免疫化学变化，海马和视网膜，为观察到的表型提供了基础。
Microtubules play an important role in establishing cellular architecture. Neuronal microtubules are considered to have a role in dendrite and axon formation, Different portions of the developing and adult brain microtubules are associated with different micro tubule-associated proteins (MAPs), The roles of each of the different MAPs are not well understood, One of these proteins, MAP1B, is expressed in different portions of the brain and has been postulated to have a role in neuronal plasticity and brain development, To ascertain the role of MAP1B, we generated mice which carry an insertion in the gene by gene-targeting methods, Mice which are homozygous for the modification die during embryogenesis. The heterozygotes exhibit a spectrum of phenotypes including slower growth rates, lack of visual acuity in one or both eyes, and motor system abnormalities, Histochemical analysis of the severely affected mice revealed that their Purkinje cell dendritic processes are abnormal, do not react with MAP1B antibodies, and show reduced staining with MAP1A antibodies, Similar histological and immunochemical changes were observed in the olfactory bulb, hippocampus, and retina, providing a basis for the observed phenotypes.