Cerebellar abnormalities in the disabled (mdab1-1) mouse

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 devel opment of the cerebrum, hippocampus, and cerebellum. Here we describe a num ber of histologic abnormalities in the cerebellum of the mdab1-1 mouse. The re is a complete absence of foliation, and most Purkinje cells are clumped in central clusters. However, lamination appears to develop normally in are as 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 Purk inje 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 sug gest that the development of the mdab1-1 cerebellum parallels the developme nt of reeler. The reeler gene encodes an extracellular protein (Reelin) tha t 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 pathw ay or downstream of Reelin, leading to the transformation of embryonic Purk inje cell clusters into the adult parasagittal bands. J. Comp. Neurol. 402: 238-251, 1998. (C) 1998 Wiley-Liss, Inc.