TY - JOUR
T1 - DSCAM
T2 - A novel member of the immunoglobulin superfamily maps in a Down syndrome region and is involved in the development of the nervous system
AU - Yamakawa, Kazuhiro
AU - Huo, Yong Kang
AU - Haendel, Melissa A.
AU - Hubert, René
AU - Chen, Xiao Ning
AU - Lyons, Gary E.
AU - Korenberg, Julie R.
N1 - Funding Information:
This research was supported by grants from the National Institute of Health (NICHD #PO1 HD17449 and NHBLI #RO1 HL50025 to J.R.K. and NICHD #29471 to G.E.L.), and the Department of Energy (#DE-FG03-92ER61402) to J.R.K. J.R.K. holds the Geri & Richard Brawerman Chair in Molecular Genetics. M.A.H. was supported by NIH GMO 7507-18. G.E.L. was supported by a grant from the American Heart Association Wisconsin Affiliate.
PY - 1998/2
Y1 - 1998/2
N2 - 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.
AB - 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.
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U2 - 10.1093/hmg/7.2.227
DO - 10.1093/hmg/7.2.227
M3 - Article
C2 - 9426258
AN - SCOPUS:0031964775
SN - 0964-6906
VL - 7
SP - 227
EP - 237
JO - Human molecular genetics
JF - Human molecular genetics
IS - 2
ER -