DSCAM: a novel member of the immunoglobulin superfamily maps in a Down syndrome region and is involved in the development of the nervous system
DSCAM: a novel member of the immunoglobulin superfamily maps in a Down syndrome region and is involved in the development of the nervous system
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DOI：
10.1093/hmg/7.2.227
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发表时间：
1998-02-01
影响因子：
3.5
通讯作者：
Korenberg, JR
中科院分区：
文献类型：
--
作者：
Yamakawa, K;Huo, YK;Korenberg, JR
唐氏综合征（Down syndrome，DS）是导致智力低下的主要原因之一，其特征是大脑皮层神经解剖学、神经化学和功能的细微异常。（唐氏综合征细胞粘附分子），现已从染色体带21q22.2-22.3分离，同源性搜索表明，推定的DSCAM蛋白是免疫球蛋白（IG）超家族的新成员，其代表一类新的神经细胞粘附分子。cDNA序列表明选择性剪接并预测两种蛋白质同种型，两者都含有10个Ig-C2结构域，其中9个在N-末端，第10个位于下面的6个纤连蛋白III结构域阵列的结构域4和5之间，有或没有下面的跨膜和胞内结构域，北方分析显示主要在脑中的9.7、8.5和7.6kb的转录物。这些转录物在成年脑的亚结构中差异表达。DSCAM基因的小鼠同源物的组织原位杂交分析揭示了在神经元分化时在神经系统内在神经管、皮质、海马、髓质、脊髓和大多数神经嵴衍生组织中的广泛表达。鉴于其在21号染色体上的位置，DSCAM在中枢神经系统和神经嵴中的特异性表达，以及与神经迁移、分化和突触功能相关分子的同源性，我们认为DSCAM参与了神经分化，并参与了DS的中枢和外周神经系统缺陷。
Down syndrome (DS), a major cause of mental retardation, is characterized by subtle abnormalities of cortical neuroanatomy, neurochemistry and function, Recent work has shown that chromosome band 21q22 is critical for many of the neurological phenotypes of DS, A gene, DSCAM (Down syndrome cell adhesion molecule), has now been isolated from chromosome band 21q22.2-22.3, Homology searches indicate that the putative DSCAM protein is a novel member of the immunoglobulin (Ig) superfamily that represents a new class of neural cell adhesion molecules, The sequence of cDNAs indicates alternative splicing and predicts two protein isoforms, both containing 10 Ig-C2 domains, with nine at the N-terminus and the tenth located between domains 4 and 5 of the following array of six fibronectin III domains, with or without the following transmembrane and intracellular domains, Northern analyses reveals the transcripts of 9.7, 8.5 and 7.6 kb primarily in brain. These transcripts are differentially expressed in substructures of the adult brain, Tissue in situ hybridization analyses of a mouse homolog of the DSCAM gene revealed broad expression within the nervous system at the time of neuronal differentiation in the neural tube, cortex, hippocampus, medulla, spinal cord and most neural crest-derived tissues, Given its location on chromosome 21, its specific expression in the central nervous system and neural crest, and the homologies to molecules involved in neural migration, differentiation, and synaptic function, we propose that DSCAM is involved in neural differentiation and contributes to the central and peripheral nervous system defects in DS.