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

doi:10.18632/oncotarget.27595

Oncotarget

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

Its scope is unique. The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. The term was introduced in the inaugural Editorial, Introducing Oncotarget.

As of January 1, 2022, Oncotarget has shifted to a continuous publishing model. Papers will now be published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Subscribe to receive alerts once a paper has been published by Oncotarget.

Impact Journals, LLC is the publisher of Oncotarget: www.impactjournals.com.

Impact Journals is a member of the Wellcome Trust List of Compliant Publishers.

Impact Journals is a member of the Society for Scholarly Publishing.

On December 23, 2022, Oncotarget server experienced a DDoS attack. As a result, Oncotarget site was inaccessible for a few hours. Oncotarget team swiftly dealt with the situation and took it under control. This malicious action will be reported to the FBI.

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

PDF | Full Text | Supplementary Files | How to cite | Press Release

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

Metrics: PDF 1259 views | Full Text 1822 views | ?

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.

All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 27595

Publication Alerts

Research Papers:

Hereditary pancreatitis model by blastocyst complementation in mouse

Abstract