A differential gene expression analysis was first performed to identify underlying differences that may account for the various endophenotypes of the selected lines and to initiate an exploration for potential molecular mechanisms that could be related to the physiological differences previously observed in the DS of HAP and LAP mice (Fritz et al. 2019). Of the 13,870 transcripts identified, 2,108 of these were found to be significantly differentially expressed between the lines (FDR<0.05). Table 1 lists the top 20 differentially expressed proteins in HAP relative to LAP mice. Although it is not feasible to validate all the differences identified by RNA-sequencing, we confirmed that C5ar2 (ANOVA: Line, F(1,20)=67.3, p<0.0001; Sex, F(1,20)=3.28, p=0.09; Interaction, F(1,20)=3.37, p=0.08) and Pla2g3 (ANOVA: Line, F(1,20=54.8, p<0.0001; Sex, F(1,20)=3.00, p=0.10; Interaction, F(1,20)=3.08, p=0.09) are increased in HAP mice relative to LAP mice and Kcnj15 (ANOVA: Line, F(1,19)=70.5, p<0.0001; Sex, F(1,19)=0.0156, p=0.90; Interaction, F(1,19)=0.0838, p=0.78) and Ubc (ANOVA: Line, F(1,20)=85.5, p<0.0001; Sex, F(1,20)=0.225, p=0.64; Interaction, F(1,20)=0.0145, p=0.91) are decreased in HAPs relative to LAPs using RT-qPCR (Supplementary Figure 3).
