Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:DSCAM: a novel member of the immunoglobulin superfamily maps in a Down syndrome region and is involved in the development of the nervous system. 942 58

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.
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PMID:Down syndrome cell adhesion molecule is conserved in mouse and highly expressed in the adult mouse brain. 1185 73

The Down syndrome cell adhesion molecule (Dscam) is a protein overexpressed in the brains of Down syndrome patients and implicated in mental retardation. Dscam is involved in axon guidance and branching in Drosophila, but cellular roles in vertebrates have yet to be elucidated. To understand its role in vertebrate development, we cloned the zebrafish homolog of Dscam and showed that it shares high amino acid identity and structure with the mammalian homologs. Zebrafish dscam is highly expressed in developing neurons, similar to what has been described in Drosophila and mouse. When dscam expression is diminished by morpholino injection, embryos display few neurons and their axons do not enter stereotyped pathways. Zebrafish dscam is also present at early embryonic stages including blastulation and gastrulation. Its loss results in early morphogenetic defects. dscam knockdown results in impaired cell movement during epiboly as well as in subsequent stages. We propose that migrating cells utilize dscam to remodel the developing embryo.
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PMID:The zebrafish down syndrome cell adhesion molecule is involved in cell movement during embryogenesis. 1570 57

Down syndrome cell adhesion molecule (DSCAM) plays important roles in the regulation of synaptogenesis, neurite outgrowth, axon guidance and synapse formation. Overexpression of DSCAM in Down syndrome (DS) may be involved in the pathogenesis of mental retardation through an inhibitory action on synaptogenesis/neurite outgrowth, and in the precocious dementia associated with an amyloid precursor protein (APP) dosage effect with enhanced plaque formation. In this report we examined the expression of DSCAM in the cerebral cortex of APP transgenic mice versus age-matched wild-type mice. We found that the level of DSCAM expression increased with increasing age in both groups of mice, up to a maximum at 3 months old. The level of DSCAM expression in APP transgenic mice was significantly higher than in the age-matched wild types. We propose that overexpression of DSCAM in the cerebral cortex might play an important role in the learning and memory defects of APP transgenic mice.
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PMID:Expression and significance of DSCAM in the cerebral cortex of APP transgenic mice. 2124 73

Fragile X syndrome is caused by the loss of Fragile X mental retardation protein (FMRP), an RNA-binding protein that suppresses protein translation. We found that FMRP binds to Down syndrome cell adhesion molecule (Dscam) RNA, a molecule that is involved in neural development and has been implicated in Down syndrome. Elevated Dscam protein levels in FMRP null Drosophila and in flies with three copies of the Dscam gene both produced specific and similar synaptic targeting errors in a hard-wired neural circuit, which impaired the flies' sensory perception. Reducing Dscam levels in FMRP null flies reduced synaptic targeting errors and rescued behavioral responses. Our results indicate that excess Dscam protein may be a common molecular mechanism underlying altered neural wiring in intellectual disabilities such as Fragile X and Down syndromes.
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PMID:Overexpression of Down syndrome cell adhesion molecule impairs precise synaptic targeting. 2371 68