Next, we asked whether stimulation of App transcription in mouse neuron/glia cultures is also mediated by the AP-1 dependent activation of the mouse App promoter. Comparison of the human APP and mouse App promoter sequences revealed that the AP-1 binding sequence is conserved evolutionary (Fig. 6E). Using a guide RNA for the AP-1 binding sequence in the mouse App promoter, we found that CRISPRi significantly suppressed APP mRNA and protein levels and decreased Aβ40 and Aβ42 secretion in mouse neuron/glia cultures (Fig. 6F–6H, S7E–S7G). Thus, the same signaling pathway controls Aβ-production in human and mouse neurons.
