Disease relevance of Dscam

• Down Syndrome Cell Adhesion molecule (DSCAM) is a member of the immunoglobulin superfamily, and represents a novel class of neuronal cell adhesion molecules [1].

Psychiatry related information on Dscam

• 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 [2].

High impact information on Dscam

• A gene, DSCAM (Down syndrome cell adhesion molecule), has now been isolated from chromosome band 21q22.2-22 [3].
• 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 [3].
• DSCAM: a novel member of the immunoglobulin superfamily maps in a Down syndrome region and is involved in the development of the nervous system [3].
• 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 [3].
• 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 [3].

Biological context of Dscam

• Dscam, a novel cell-adhesion molecule belonging to the Ig-superfamily mediates homophilic intercellular adhesion and is expressed abundantly in the nervous system during development [4].
• Immunohistochemical studies showed that during embryonic development of mice, mouse Dscam is expressed throughout the neuronal tissues and also in nonneuronal tissues such as lung, liver, and limb buds [4].
• In mouse, DSCAM is located on 16C, the syntenic region for human chromosome band 21q22 and also the region duplicated in mouse DS models [1].
• Sequence analysis of the human DSCAM cDNA predicted at least 33 exons that are distributed over 840 kb [1].
• To evaluate the role of the axonal guidance molecule DSCAM in CNS connectivity, we generated a lacZ reporter construct, Pr1.8-betagal, containing a 1.8kb fragment of the human DSCAM promoter region, and analyzed its expression in four E12.5 transgenic mouse embryos [5].

Anatomical context of Dscam

• Dscam is also expressed ventrally in the adult spinal cord [2].
• In adult brain Dscam expression is predominant in the cerebellum, hippocampus, and olfactory bulb [4].
• DSCAM: an endogenous promoter drives expression in the developing CNS and neural crest [5].
• In the cerebellum, DSCAM is stronger in the Purkinje cells and DSCAML1 in the granule cells [6].

Analytical, diagnostic and therapeutic context of Dscam

• Immunofluorescence double labeling of hippocampal and cerebellar primary cultures revealed that Dscam is associated with axonal and dendritic processes [4].

References