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World J Stem Cells. Aug 26, 2015; 7(7): 1054-1063
Published online Aug 26, 2015. doi: 10.4252/wjsc.v7.i7.1054
Rat embryonic stem cells create new era in development of genetically manipulated rat models
Kazushi Kawaharada, Masaki Kawamata, Takahiro Ochiya
Kazushi Kawaharada, Research and Development Division, DS Pharma Biomedical Co. Ltd., Osaka 564-0053, Japan
Masaki Kawamata, Takahiro Ochiya, Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo 104-0045, Japan
Author contributions: Kawaharada K, Kawamata M and Ochiya T contributed to this paper.
Conflict-of-interest statement: Kazushi Kawaharada is an employee of DS Pharma Biomedical Co., Ltd. The other authors declared no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Takahiro Ochiya, Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. tochiya@ncc.go.jp
Telephone: +81-3-35422511 Fax: +81-3-55650727
Received: August 22, 2014
Peer-review started: August 23, 2014
First decision: September 28, 2014
Revised: May 29, 2015
Accepted: July 16, 2015
Article in press: July 18, 2015
Published online: August 26, 2015
Processing time: 369 Days and 23.7 Hours
Abstract

Embryonic stem (ES) cells are isolated from the inner cell mass of a blastocyst, and are used for the generation of gene-modified animals. In mice, the transplantation of gene-modified ES cells into recipient blastocysts leads to the creation of gene-targeted mice such as knock-in and knock-out mice; these gene-targeted mice contribute greatly to scientific development. Although the rat is considered a useful laboratory animal alongside the mouse, fewer gene-modified rats have been produced due to the lack of robust establishment methods for rat ES cells. A new method for establishing rat ES cells using signaling inhibitors was reported in 2008. By considering the characteristics of rat ES cells, recent research has made progress in improving conditions for the stable culture of rat ES cells in order to generate gene-modified rats efficiently. In this review, we summarize several advanced methods to maintain rat ES cells and generate gene-targeted rats.

Keywords: Embryonic stem cells; Transgenic rat

Core tip: Rat embryonic stem (ES) cells are thought to be an essential tool for creating transgenic rats. Since the method for establishing rat ES cells using signaling inhibitors was reported, numerous approaches have been made to propagate rat ES cells efficiently. Additionally, recent investigations have demonstrated the usefulness of the signal inhibitors for microinjection. In this review, we summarize the several advanced methods to maintain rat ES cells and generate gene-targeted rats.