A bioluminescent mouse model of proliferation to highlight early stages of pancreatic cancer. A suitable tool for preclinical studies

Transgenic mouse models designed to recapitulate genetic and pathologic aspects of cancer are usefulto study early stages of disease as well as its progression. Among several, two of the most sophis-ticated models for pancreatic ductal adenocarcinoma (PDAC) are the LSL-KrasG12D/+;Pdx-1-Cre (KC)and LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre (KPC) mice, in which the Cre-recombinase regulated by apancreas-specific promoter activates the expression of oncogenic Kras alone or in combination witha mutant p53, respectively. Non-invasive in vivo imaging offers a novel approach to preclinical stud-ies introducing the possibility to investigate biological events in the spatio/temporal dimension. Werecently developed a mouse model, MITO-Luc, engineered to express the luciferase reporter gene in cellsundergoing active proliferation. In this model, proliferation events can be visualized non-invasively bybioluminescence imaging (BLI) in every body district in vivo. Here, we describe the development andcharacterization of MITO-Luc-KC- and -KPC mice. In these mice we have now the opportunity to followPDAC evolution in the living animal in a time frame process. Moreover, by relating in vivo and ex vivoBLI and histopathological data we provide evidence that these mice could represents a suitable tool forpancreatic cancer preclinical studies. Our data also suggest that aberrant proliferation events take placeearly in pancreatic carcinogenesis, before tumour appearance.