Combined genetic knockdown of MEK1 and MEK2 can prevent onset of pancreatitis. (A) CP protocol after initiation of shRNA expression. (B) Immunoblot for levels of phosphorylated MAPK, total MAPK, and the loading control HSP90. The ratio of the band intensities of phosphorylated/total MAPK is indicated under each lane. (C) Representative histology of each genotype with quantitation for amylase and picrosirius positive tissue (D) and immune cell infiltration (E). Blue bars represent Ptf1a+/Cre control mice; red bars indicate shMEK1/2 mice, n ≥ 3 for all comparisons. (F) qRT-PCR analysis of acinar markers Amy2b, Ptf1a, and Mist1 and ductal marker Krt19, n = 4. (G) Acinar cell explants embedded in Matrigel were imaged at Day 0 and Day 3. (H) Acinar to ductal cyst conversion on Day 3 as quantitated by a blinded observer, n = 3. (I) Relative pancreas mass, defined by percentage pancreas weight over body weight, n = 4 for all groups. Error bars represent mean with standard deviation. Scale bars = 100 μm for panels, 50 μm for insets.