WEAVER MUTANT MOUSE CEREBELLUM - DEFECTIVE NEURONAL MIGRATION SECONDARY TO ABNORMALITY OF BERGMANN GLIA
WEAVER MUTANT MOUSE CEREBELLUM - DEFECTIVE NEURONAL MIGRATION SECONDARY TO ABNORMALITY OF BERGMANN GLIA
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DOI：
10.1073/pnas.70.1.240
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发表时间：
1973-01-01
影响因子：
11.1
通讯作者：
SIDMAN, RL
中科院分区：
文献类型：
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作者：
RAKIC, P;SIDMAN, RL
先前的研究表明，在常染色体突变weaver,wv纯合的小鼠小脑中，大多数有丝分裂后颗粒细胞神经元在出生后的前两周内死亡，死亡位置靠近其在外部颗粒层的起源位置。通过电子显微镜和放射自显影对受影响较轻的杂合子进行的分析表明，颗粒细胞死亡发生在细胞发生几天后，并且是由于其体细胞未能穿过分子层迁移到颗粒层而继发的。这种迁移缺陷反过来似乎继发于迄今为止未被识别的伯格曼神经胶质细胞的疾病，这种细胞通常指导年轻神经元的迁移。在+/wv小脑中，伯格曼神经胶质突起增大且口径不规则、电透明且通常呈空泡状；在wv/wv中，伯格曼细胞突起几乎不存在。主要的遗传异常仍不清楚，但基因剂量效应（首次在哺乳动物神经突变体的细胞水平上被识别）表明，尽管神经元死亡是最突出和临床相关的表型表达，但伯格曼胶质细胞异常实际上可能更接近于wv遗传基因座的主要细胞目标。
Previous work showed that in cerebella of mice homozygous for the autosomal mutation weaver,wv, most postmitotic granule cell neurons die during the first 2 weeks after birth close to their site of genesis in the external granular layer. Analysis of the less severely affected heterozygotes by electron microscopy and autoradiography indicates that granule cell death occurs several days after cell genesis and is secondary to failure of their somas to migrate across the molecular layer to the granular layer. This migration defect in turn appears secondary to a hitherto unrecognized disorder of Bergmann glial cells, the cells that normally guide the young neurons in their migration. In +/wvcerebella, Bergmann glial processes are enlarged and irregular in caliber, electronlucent, and often vacuolated; inwv/wv, Bergmann cell processes are almost absent. The primary genetic abnormality remains undefined, but the gene dosage effect, here recognized at a cellular level for the first time in a mammalian neurological mutant, suggests that even though neuronal death serves as the most prominent and clinically relevant phenotypic expression, the Bergmann glial abnormality may actually be closer to the primary cellular target of thewvgenetic locus.