Adam Knox Indiana University-Purdue University Indianapolis
Faculty Sponsor(s): Randall Roper Indiana University-Purdue University IndianapolisDown syndrome (DS) is the most common trisomic chromosomal disorder in humans, resulting from three copies of human chromosome 21 (Hsa21) and occurs in about 1 out of 700 US births. Triplication of Hsa21 results in up-regulation and down-regulation of Hsa21 genes, not always consistent with the trisomic gene dosage level, as well as genome-wide dysregulation of transcription. These genetic imbalances manifest in a plethora of phenotypes including abnormal skeletal development and disrupted bone homeostasis that contribute to the increased incidence of osteoporosis and osteopenia in individuals with DS. A primary therapeutic target for these skeletal deficits, as well as many other DS related phenotypes, is DYRK1A, a gene triplicated in DS. Reduction of Dyrk1a copy number to euploid level in 6 and 11 week old Ts65Dn mice resulted in restoration of many trabecular and cortical measures, although, Dyrk1a normalization was significantly less effective in 11 week old mice. These results confirm the importance of Dyrk1a’s role in aberrant skeletal phenotypes in DS, but suggest this role may not be consistent throughout development.
When & Where
Gallahue Hall 105