title: DSCAM: a novel member of the immunoglobulin superfamily maps in a Down syndrome region and is involved in the development of the nervous system.
abstract: 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.
authors.affiliation: Division of Medical Genetics, Cedars-Sinai Research Institute/UCLA, Los Angeles, CA 90048-1869, USA.
authors.forename: K
authors.initials: K
authors.lastname: Yamakawa
authors.forename: Y K
authors.initials: YK
authors.lastname: Huot
authors.forename: M A
authors.initials: MA
authors.lastname: Haendelt
authors.forename: R
authors.initials: R
authors.lastname: Hubert
authors.forename: X N
authors.initials: XN
authors.lastname: Chen
authors.forename: G E
authors.initials: GE
authors.lastname: Lyons
authors.forename: J R
authors.initials: JR
authors.lastname: Korenberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D015815:Cell Adhesion Molecules; D002454:Cell Differentiation; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D004314:Down Syndrome / Q000235:genetics*; D005314:Embryonic and Fetal Development / Q000235:genetics*; D005326:Fetal Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005796:Genes; D005865:Gestational Age; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D009420:Nervous System / Q000196:embryology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics* / Q000502:physiology; D012326:RNA Splicing; D013045:Species Specificity
chemical_list: D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; C110833:DSCAM protein, human; C491735:Dscam protein, mouse; D005326:Fetal Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins