Effect of Dyrk1a inhibition on the transcriptome of embryonic hearts from the Dp1Tyb mouse model of Down syndrome using bulk RNAseq
Embryos from the Dp1Tyb mouse model for Down syndrome (DS) present with congenital heart defects similar to the heart defects seen in humans with DS. We found that genetically reducing the copy number of the Dyrk1a gene (one of the genes in 3 copies in DS) from 3 to 2, normalised some of the transcriptomic changes in Dp1Tyb embryonic hearts and rescued congenital heart defects. Here we treated pregnant mice carrying Dp1Tyb and wild-type (WT) embryos with a Dyrk1a pharmacological inhibitor (Leucettinib-21 or L21) or an inactive isomer (Iso-L21) to study the effect of L21 on the transcriptome of Dp1Tyb and WT embryonic hearts. Overall design: C56BL/6J females were set up in timed matings  with Dp1Tyb males and were treated daily by oral gavage with 30mg/kg of L21 or Iso-L21 from embryonic day 5.5 to E13.5. 20 embryonic hearts were used for this study; five biological repeats per condition (4 conditions: 2 genotypes treated with L21 or iso-L21) were used for bulk RNAseq.