D'Arcangelo G, Miao G G, Chen S C, Soares H D, Morgan J I, Curran T
Roche Institute of Molecular Biology, Hoffman La Roche, Nutley, New Jersey 07110, USA.
Nature. 1995 Apr 20;374(6524):719-23. doi: 10.1038/374719a0.
The autosomal recessive mouse mutation reeler leads to impaired motor coordination, tremors and ataxia. Neurons in affected mice fail to reach their correct locations in the developing brain, disrupting the organization of the cerebellar and cerebral cortices and other laminated regions. Here we use a previously characterized reeler allele (rl(tg)) to close a gene, reelin, deleted in two reeler alleles. Normal but not mutant mice express reelin in embryonic and postnatal neurons during periods of neuronal migration. The encoded protein resembles extracellular matrix proteins involved in cell adhesion. The reeler phenotype thus seems to reflect a failure of early events associated with brain lamination which are normally controlled by reelin.
常染色体隐性小鼠突变“reeler”会导致运动协调受损、震颤和共济失调。受影响小鼠的神经元在发育中的大脑中无法到达其正确位置,从而破坏了小脑和大脑皮层以及其他分层区域的组织结构。在这里,我们使用一个先前已鉴定的“reeler”等位基因(rl(tg))来克隆一个在两个“reeler”等位基因中缺失的基因——reelin。正常小鼠而非突变小鼠在神经元迁移期间的胚胎期和出生后神经元中表达reelin。编码的蛋白质类似于参与细胞黏附的细胞外基质蛋白。因此,“reeler”表型似乎反映了与脑分层相关的早期事件的失败,而这些事件通常受reelin控制。