The H1-promoter-driven shRNA cassettes were constructed by annealing two primers containing the 19-nt sense and reverse complementary targeting sequences with a 9-nucleotide loop -TTCAAGAGA-and flanking Mlu1 and Cla1 cloning sites (the sequences of shRNA were shown in the supporting information Table S1 ), and then cloned into the 39-end of the H1 promoter in the LVTHM plasmid [35, 36] . The sequences of the insertions were confirmed by DNA sequencing.