Hereditary pancreatitis model by blastocyst complementation in mouse

Ayumu Asai, Masamitsu Konno, Koichi Kawamoto, Ayako Isotani, Masaki Mori, Hidetoshi Eguchi, Yuichiro Doki, Takahiro Arai, Hideshi Ishii

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Abstract

The application of pluripotent stem cells is expected to contribute to the elucidation of unknown mechanism of human diseases. However, in vitro induction of organ-specific cells, such as pancreas and liver, is still difficult and the reproduction of their disorders in a model has been unfeasible. To study the mechanism of human hereditary pancreatitis (HP), we here performed the blastocyst complementation (BC) method. In the BC method, mouse embryonic stem (ES) cells harboring CRISPR/CAS9-mediated mutations in the Prss1 gene were injected into blastocysts with deficient Pdx1 gene, which is a critical transcription factor in the development of pancreas. The results showed that trypsin was activated extremely in Prss1-mutant mice. This implied that the mouse phenotype mimics that of human HP and that the BC method was useful for the reproduction and study of pancreatic disorders. The present study opens the possibility of investigating uncharacterized human diseases by utilizing the BC method.

Original languageEnglish
Pages (from-to)2061-2073
Number of pages13
JournalOncotarget
Volume11
Issue number22
DOIs
Publication statusPublished - Jun 1 2020

All Science Journal Classification (ASJC) codes

  • Oncology

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    Asai, A., Konno, M., Kawamoto, K., Isotani, A., Mori, M., Eguchi, H., Doki, Y., Arai, T., & Ishii, H. (2020). Hereditary pancreatitis model by blastocyst complementation in mouse. Oncotarget, 11(22), 2061-2073. https://doi.org/10.18632/oncotarget.27595