Barlow G M, Micales B, Lyons G E, Korenberg J R
Department of Medical Genetics, Cedars-Sinai Medical Center and UCLA, 90048, USA.
Cytogenet Cell Genet. 2001;94(3-4):155-62. doi: 10.1159/000048808.
Down Syndrome (DS) is a major cause of mental retardation and is associated with characteristic well-defined although subtle brain abnormalities, many of which arise after birth, with particular defects in the cortex, hippocampus and cerebellum. The neural cell adhesion molecule DSCAM (Down syndrome cell adhesion molecule) maps to 21q22.2-->q22.3, a region associated with DS mental retardation, and is expressed largely in the neurons of the central and peripheral nervous systems during development. In order to evaluate the contribution of DSCAM to postnatal morphogenetic and cognitive processes, we have analyzed the expression of the mouse DSCAM homolog, Dscam, in the adult mouse brain from 1 through 21 months of age. We have found that Dscam is widely expressed in the brain throughout adult life, with strongest levels in the cortex, the mitral and granular layers of the olfactory bulb, the granule cells of the dentate gyrus and the pyramidal cells of the CA1, CA2 and CA3 regions, the ventroposterior lateral nuclei of the thalamus, and in the Purkinje cells of the cerebellum. Dscam is also expressed ventrally in the adult spinal cord. Given the homology of DSCAM to cell adhesion molecules involved in development and synaptic plasticity, and its demonstrated role in axon guidance, we propose that DSCAM overexpression contributes not only to the structural defects seen in these regions of the DS brain, but also to the defects of learning and memory seen in adults with DS.
唐氏综合征（DS）是智力发育迟缓的主要原因，与特征明确但细微的脑部异常有关，其中许多异常在出生后出现，特别是在皮质、海马体和小脑中存在特定缺陷。神经细胞黏附分子DSCAM（唐氏综合征细胞黏附分子）定位于21q22.2→q22.3，该区域与唐氏综合征智力发育迟缓相关，并且在发育过程中主要在中枢和外周神经系统的神经元中表达。为了评估DSCAM对出生后形态发生和认知过程的作用，我们分析了小鼠DSCAM同源物Dscam在1至21月龄成年小鼠脑中的表达情况。我们发现，Dscam在成年期的整个大脑中广泛表达，在皮质、嗅球的二尖瓣层和颗粒层、齿状回的颗粒细胞以及CA1、CA2和CA3区域的锥体细胞、丘脑腹后外侧核以及小脑的浦肯野细胞中表达水平最高。Dscam在成年脊髓的腹侧也有表达。鉴于DSCAM与参与发育和突触可塑性的细胞黏附分子具有同源性，并且其在轴突导向中已被证实的作用，我们提出DSCAM的过表达不仅导致唐氏综合征患者大脑这些区域出现结构缺陷，还导致成年唐氏综合征患者出现学习和记忆缺陷。
