To assess the impact of mir-17~92 deletion on the development and progression of precursor precancerous PanIN lesions, we crossed mir-17~92flox/flox, Ptf1a-Cre mice onto the LSL-KrasG12D background . Breeding pairs were designed to cross mir-17~92flox/wt, LSL-KrasG12D mice with mir-17~92flox/wt, Ptf1a-Cre mice in order to generate littermate mir-17~92wt/wt, LSL-KrasG12D, Ptf1a-Cre and mir-17~92flox/flox, LSL-KrasG12D, Ptf1a-Cre mice (hereafter ‘KC’ and ‘17KC’). Littermate KC and 17KC animals were maintained until four or nine months of age and subsequently euthanized to obtain pancreata for histological analysis. At four months of age, the tissue area occupied by PanIN lesions was not significantly different between the two groups as illustrated by hematoxylin and eosin staining and quadchrome staining (Figure 1A–1D, 1I). However, the extent of normal acinar tissue was significantly greater in the pancreata of 17KC mice (Figure 1I). Nine month-old KC mice displayed higher PanIN burdens compared to younger KC mice and nine month-old 17KC littermates (Figure 1E–1I). In contrast to the trend observed in KC mice, we observed that the pancreata of nine month-old 17KC mice exhibited less PanIN tissue and more healthy acinar tissue by area than four month-old 17KC mice (Figure 1F, 1H, 1I). Of note, PanIN lesions in KC and 17KC pancreata demonstrate no significant differences in proliferation or apoptosis markers and no differences were observed in the proliferative rate of adjacent acinar tissue (Supplementary Figure 3). Together, these data suggest that loss of mir-17~92 impairs the maintenance of PanIN lesions.