Down syndrome (DS) occurs as a result of Trisomy 21 and is among the most complicated genetic conditions compatible with human survival. The Reeves laboratory complements genetic analyses in human beings with the creation and characterization of mouse models to understand why and how gene dosage imbalance disrupts development in DS. These models then provide a basis to explore therapeutic approaches to amelioration of DS features. We use chromosome engineering in ES cells to create defined dosage imbalance in order to localize the genes contributing to these anomalies and to test directly hypotheses concerning Down syndrome "critical regions" on human chromosome 21.

Quantitative phenotypic assays that we have developed give a precise and sensitive readout of the relative effects on phenotype when overlapping subsets of genes are at dosage imbalance. Developmental analyses of these traits are underway to identify the timing and location of divergence between trisomic and euploid fetuses. More...

Roger H. Reeves, Ph.D. Professor Johns Hopkins Univ. Schl. of Medicine Department of Physiology and McKusick-Nathans Institute for Genetic

Medicine Biophysics 201 725 North Wolfe Street Baltimore, MD 21025 TEL (410) 955-6621 FAX (443) 287-0508 rreeves@jhmi.edu