Identifying Influential Trisomic Genes that Contribute to Skeletal Phenotypes in Down Syndrome

Matthew Blackwell Indiana University-Purdue University Indianapolis
Faculty Sponsor(s): Randall Roper Indiana University-Purdue University Indianapolis
Bone abnormalities including osteoporosis result from skeletal developmental deficits caused by Down syndrome (DS). DS mouse models have been shown to recapitulate deficits seen in humans with DS. The Ts65Dn mouse model has ~100 trisomic genes, and trisomic Dyrk1a has been shown to have a causal role in bone phenotypes. Similar skeletal phenotypes and sexual dimorphism in how these phenotypes occur has been identified in Dp1Tyb mice (148 trisomic genes). A mouse mapping panel has been created from the contiguous segmental trisomic regions included in the Dp1Tyb mouse model and these Dp2Tyb, Dp3Tyb, and Dp9Tyb mouse models can be used to identify trisomic genes or regions involved in specific bone phenotypes. We hypothesize that trisomic genes in addition to Dyrk1a make important contributions to the skeletal traits characterized in DS. To test this hypothesis, we performed structural and mechanical analyses of femurs from male and female Dp2Tyb, Dp3Tyb, and Dp9Tyb mice. Trisomic candidate genes present in these strains include Dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1a) on Dp3Tyb, Regulator of calcineurin 1 (Rcan1) and Runt related transcription factor 1 (Runx1) on Dp2Tyb, and Amyloid beta precursor protein (App) and Nuclear receptor interacting protein 1 (Nrip1) on Dp9Tyb, genes that may play important roles in skeletal formation and maintenance. This research will provide insight into the complex genetic and phenotypic interactions that contribute to the skeletal abnormalities found in DS.
Oral Presentation

When & Where

10:00 AM
Gallahue Hall 105