Browsing by Subject "Trisomy"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    A new Down syndrome rat model races forward
    (Elsevier, 2022) Roper, Randall J.; Goodlett, Charles R.; Biology, School of Science
    Animal models of Down syndrome (DS) provide an essential resource for understanding genetic, cellular, and molecular contributions to traits associated with trisomy 21 (Ts21). Recent genetic enhancements in the development of DS models, including the new TcHSA21rat model (Kazuki et al.), have potential to transform our understanding of and potential therapies for Ts21.
  • Thumbnail Image
    Item
    [Letter to the editor] PCR prescreen for genotyping the Ts65Dn mouse model of Down syndrome
    (Future Medicine, 2018-04-03) Lorenzi, Hernan; Duvall, Nichole; Cherry, Sheila M.; Reeves, Roger H.; Roper, Randall J.; Biology, School of Science
  • Thumbnail Image
    Item
    Sexually dimorphic DYRK1A overexpression on postnatal day 15 in the Ts65Dn mouse model of Down syndrome: Effects of pharmacological targeting on behavioral phenotypes
    (Elsevier, 2022) Hawley, Laura E.; Prochaska, Faith; Stringer, Megan; Goodlett, Charles R.; Roper, Randall J.; Biology, School of Science
    The neurotypical spatiotemporal patterns of gene expression are disrupted in Down syndrome (DS) by trisomy of human chromosome 21 (Hsa21), resulting in altered behavioral development and brain circuitry. The Ts65Dn DS mouse model exhibits similar phenotypes to individuals with DS due to three copies of approximately one-half of the genes found on Hsa21. Dual-specificity Tyrosine Phosphorylation-regulated Kinase 1a (Dyrk1a), one of these triplicated genes, is an attractive target to normalize brain development due to its influence in cellular brain deficits seen in DS. We hypothesized that postnatal development of DYRK1A expression is dysregulated in trisomic animals, and found significant overexpression of DYRK1A in the hippocampus, cerebral cortex, and cerebellum at postnatal day (P) 15 in male—but not female—Ts65Dn mice. We then hypothesized the existence of sex-dependent effects of trisomy on neurobehavioral attributes during P16-17, and that administration of a DYRK1A inhibitor (CX-4945, ∼75mg/kg) beginning on P14 would normalize aberrant behavior in trisomic animals. Both male and female trisomic mice given control injections of phosphate buffered saline (PBS) displayed sustained levels of locomotor activity over a 10-minute test in contrast to the PBS-treated euploid animals that showed significant within-session habituation. Trisomic animals were more persistent in choosing to remain in home shavings in a preference test. Treatment with CX-4945 failed to confirm therapeutic effects. CX-4945 prevented growth, and both CX-4945 and its 10% dimethyl sulfoxide vehicle affected locomotor activity in trisomic and euploid groups, indicating a non-specific disruption of behavior. Despite the negative outcomes for CX-4945, the novel demonstration of sexually dimorphic DYRK1A expression in trisomic animals at P15 supports the broader hypothesis that overexpression of trisomic genes in DS can vary with age, sex, and brain region. Identifying the developmental timing of periods of dysregulated DYRK1A may be important for understanding individual differences in neurodevelopmental trajectories in DS and for developing effective therapeutic interventions targeting DYRK1A.