Down Syndrome (DS), the most common cause of mental retardation, is a genetic disorder caused by the presence of either all or part of an extra human chromosome 21 (HSA21) (1). Phenotypic traits commonly associated with DS include congenital heart disease, short stature, decreased muscle tone, and hearing loss. DS patients also show an increased risk of developing leukemia or early onset Alzheimer disease. Down Syndrome Cell Adhesion Molecule (DSCAM) is an HSA21 axon guidance molecule involved in the development of the nervous system (2).

In murine models of DS, the DSCAM homologue is expressed in adult and embryonic brain and heart where it modulates inter-cell connections (1). In mouse brain, three copies of DSCAM result in an overexpression of the protein, which contributes to a severe disorganization of dendritic spines. Normally, dendritic spines develop postnatally and provide the necessary plasticity required for cognition (1). In mouse heart, DSCAM regulates the transduction of electro-mechanical impulses. Abnormal expression of DSCAM results in defects in the septum and atrioventricular canal (3), which contribute to cardiomyopathy (J. Korenberg, unpublished data). Further investigation of the role mouse DSCAM plays during development may provide an explanation for the brain and cardiovascular abnormalities associated with DS.

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