Disease relevance of DSCAM

• Down syndrome cell adhesion molecule DSCAM mediates homophilic intercellular adhesion [1].
• These data suggest implication of DSCAM in the adult neurogenesis of primate hippocampus upregulated after ischemia [2].
• However, in the subgranular zone, cerebral ischemia led to a marked increase of DSCAM-positive cells on days 9 and 15 [2].
• The present case provides further support to the concept that there exists Down syndrome-associated congenital heart disease gene(s) on chromosome 21q22 and that over-expression of DSCAM may contribute to the cardiac defects of Down syndrome [3].
• In vivo studies have begun to suggest models for use of Dscam diversity in neuron-target recognition, axon fasciculation, and neuron self-recognition [4].

Psychiatry related information on DSCAM

• The overexpression of DSCAM may also play a role in the mental retardation and the precocious dementia of DS patients, although the mechanism of neuronal dysfunction is undetermined [5].

High impact information on DSCAM

• Alternative splicing of Dscam mRNA potentially generates 38016 isoforms of a cell-surface recognition protein of the immunoglobulin superfamily [6].
• Furthermore, expression of the cytoplasmic domain of DSCAM induces a morphological change in cultured cells that is JNK-dependent [7].
• The Down syndrome cell adhesion molecule (DSCAM) is a member of the immunoglobulin superfamily that maps to a Down syndrome region of chromosome 21q22.2-22 [7].
• DSCAM upregulation was seen in two cell types: one is immature neurons positive for polysialylated neural cell adhesion molecule or betaIII-tubulin, while another is astrocytes positive for S100beta [2].
• In contrast with approximately threefold upregulation of Dscam gene on days 5 and 7, immunoblotting and immunofluorescence analyses using specific antibodies showed a gradual decrease of DSCAM after ischemia until day 9 followed by recovery on day 15 [2].

Biological context of DSCAM

• DSCAM, a conserved gene involved in neuronal differentiation, is a member of the Ig superfamily of cell adhesion molecules [8].
• DSCAM-expressing transfectants exhibited enhanced adhesive properties, aggregating with faster kinetics and forming aggregates in a homophilic manner [1].
• DSCAM is predicted to be a transmembrane protein with a very high structural and sequence homology to Ig superfamily of cell adhesion molecules and is expressed in the developing nervous system with the highest level in fetal brain [1].
• RESULTS: apoE 3/4 genotype and E4 allele frequency in the CHD1 group were higher than those in the CHD2 group and healthy subjects, while no differences were found between CHD2 and healthy subjects [9].

Anatomical context of DSCAM

• To understand the cellular function of DSCAM protein, we transfected human DSCAM cDNA into mouse fibroblast L cells and analysed its expression [1].
• In the control, immunofluorescence reactivity of DSCAM was detected in dentate gyrus granule cells and CA4 neurons but decreased after ischemia, being compatible with the immunoblotting data [2].
• In demented DS patients, DSCAM immunoreactivity was observed in the core and periphery of senile plaques [5].
• In DS brains, immunoreactivity for DSCAM, compared to that for controls, was enhanced in the Purkinje cells at all ages, and in the cortical neurons during adulthood [5].

Associations of DSCAM with chemical compounds

• Changes in the HmethylCmethylC angle are found to be small, with average differences on the order of 0.3+/-0.1 degrees and 0.4+/-0.2 degrees between CH3, CH2D and CH3, CHD2 isotopomers, respectively [10].
• METHODS: Sixty-eight patients with CHD younger than 55 years (CHD1), 136 patients with CHD older than 65 years (CHD2), and 136 healthy subjects were enrolled, and their plasma levels of triglyceride (TG), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) were determined [9].

Other interactions of DSCAM

• Based on its structural and functional properties and similarities to DSCAM, we suggest that DSCAML1 may be involved in formation and maintenance of neural networks [8].
• Included within the interval was the cell adhesion molecule DSCAM but not the collagen COL6A1 [3].

Analytical, diagnostic and therapeutic context of DSCAM

• On Western blot analysis, antibodies raised against recombinant DSCAM-Ig3 recognized a 198 kDa protein band in the membrane fraction of DSCAM transfected L cells [1].
• Immunohistochemistry demonstrated DSCAM in the cerebral and cerebellar white matter of both control and DS subjects, in accordance with the temporal and spatial sequence of myelination [5].

References