Gallagher E, Howell B W, Soriano P, Cooper J A, Hawkes R
Department of Anatomy and Neuroscience Research Group, Faculty of Medicine, The University of Calgary, Alberta, Canada.
J Comp Neurol. 1998 Dec 14;402(2):238-51.
A mouse homolog of the Drosophila Disabled (dab) gene, disabled-1 (mdab1), encodes an adaptor molecule that functions in neural development. Targeted disruption of the mdab1 gene (mdab1-1 mice) leads to anomalies in the development of the cerebrum, hippocampus, and cerebellum. Here we describe a number of histologic abnormalities in the cerebellum of the mdab1-1 mouse. There is a complete absence of foliation, and most Purkinje cells are clumped in central clusters. However, lamination appears to develop normally in areas where the Purkinje cells and external granular layer are closely apposed. The granular layer forms a thin rind over most of the cerebellar surface, but is subdivided by both transverse and parasagittal boundaries. The Purkinje cells, identified by anti-zebrin II in the adult or anti-calbindin in the new born mdab1-1 mutant cerebellum, form a parasagittal banding pattern, similar to but distorted compared with the wild-type design. The data suggest that the development of the mdab1-1 cerebellum parallels the development of reeler. The reeler gene encodes an extracellular protein (Reelin) that is secreted by the external granular layer. Because Reelin expression is retained in the mdab1-1 mutant mouse, mDab1 p80 may act in a parallel pathway or downstream of Reelin, leading to the transformation of embryonic Purkinje cell clusters into the adult parasagittal bands.
果蝇失能基因（dab）的小鼠同源基因——失能-1（mdab1），编码一种在神经发育中起作用的衔接分子。对mdab1基因进行靶向破坏（mdab1-1小鼠）会导致大脑、海马体和小脑发育异常。在此，我们描述了mdab1-1小鼠小脑的一些组织学异常情况。小脑完全没有脑沟回，大多数浦肯野细胞聚集在中央簇中。然而，在浦肯野细胞和外颗粒层紧密相邻的区域，分层似乎发育正常。颗粒层在小脑大部分表面形成一层薄壳，但被横向和矢状旁边界细分。在成年mdab1-1突变体小脑中通过抗zebrin II抗体或在新生小鼠中通过抗钙结合蛋白抗体鉴定出的浦肯野细胞，形成矢状旁带状模式，与野生型模式相似但有所扭曲。数据表明mdab1-1小鼠小脑的发育与reeler小鼠的发育相似。reeler基因编码一种由外颗粒层分泌的细胞外蛋白（Reelin）。由于mdab1-1突变小鼠中保留了Reelin的表达，mDab1 p80可能在与Reelin平行的途径中或在其下游起作用，导致胚胎期浦肯野细胞簇转化为成年期矢状旁带。
