Oncotarget

Research Papers:

Hereditary pancreatitis model by blastocyst complementation in mouse

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

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Oncotarget. 2020; 11:2061-2073. https://doi.org/10.18632/oncotarget.27595

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Abstract

Ayumu Asai1,2,3,*, Masamitsu Konno1,2,3,*, Koichi Kawamoto3, Ayako Isotani4, Masaki Mori3,5, Hidetoshi Eguchi3, Yuichiro Doki3, Takahiro Arai6 and Hideshi Ishii1,2

1 Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita 565-0871 Japan

2 Department of Medical Data Science, Graduate School of Medicine, Osaka University, Suita 565-0871 Japan

3 Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita 565-0871 Japan

4 Organ Developmental Engineering, Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma 630-0192 Japan

5 Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582 Japan

6 Unitech Co., Ltd., Kashiwa 277-0005 Japan

* These authors contributed equally to this work

Correspondence to:

Hideshi Ishii,email: [email protected]
Takahiro Arai,email: [email protected]

Keywords: blastocyst complementation; hereditary pancreatitis; disease-specific pluripotent stem cells; PRSS1

Received: March 01, 2020     Accepted: April 03, 2020     Published: June 02, 2020

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.


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