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Phenotyping analysis of p53 knockout mice produced by gene editing and comparison with conventional p53 knockout mice

  • Ukjin Kim
  • C-Yoon Kim
  • Hanseul Oh
  • Ji Min Lee
  • Seo-Na Chang
  • Bokyeong Ryu
  • Jin Kim
  • Han-Woong Lee
  • Jae-Hak ParkEmail author
Research Article

Abstract

Background

Knockout (KO) mice developed by homologous recombination (HR) have become useful tools to elucidate gene function. However, HR has low KO efficiency and is time-consuming, labor-intensive, and expensive. ‘Gene editing’ has received much attention for efficient genetic manipulation.

Objective

As generation of KO mice is simplified, KO mice produced by HR can be feasibly reproduced using gene editing. However, phenotyping analysis and comparison between KO mice produced by these two techniques is necessary.

Methods

We generated p53 KO mice through gene editing and compared their phenotype with the already reported HR-mediated p53 KO mice.

Results

Tumors occurred in 36 (73%) of 49 homozygous KO mice and the mean age of occurrence was 23 weeks, with lymphoma (64%) and sarcoma (23%) being the most common. Tumors were also developed in 12 heterozygous mice and the mean age of occurrence was 40 weeks, with sarcoma (54%) and lymphoma (46%) in high proportion. Homozygotes had a mean life span of 157 ± 52 days and developmental abnormalities were found in females compared to in males (P < 0.05, P < 0.001).

Conclusion

We analyzed the basic phenotype of p53 KO mice and observed no significant difference from the conventional HR-mediated p53 KO mice.

Keywords

Mouse cancer model Homologous recombination Gene editing TALEN P53 

Abbreviations

KO

Knockout

HR

Homologous recombination

Notes

Acknowledgements

This work was supported by the Ministry of Food and Drug Safety (MFDS) and the Brain Korea 21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine of Seoul National University.

Compliance with ethical standards

Conflict of interest

Ukjin Kim declares that he has no conflict of interest. C-Yoon Kim declares that he has no conflict of interest. Hansel Oh declares that she has no conflict of interest. Ji Min Lee declares that she has no conflict of interest. Seo-Na Chang declares that she has no conflict of interest. Bokyeong Ryu declares that she has no conflict of interest. Jin Kim declares that he has no conflict of interest. Han-Woong Lee declares that he has no conflict of interest. Jae-Hak Park declares that he has no conflict of interest.

Ethical approval

All experimental procedures were approved by the Institutional Animal Care and Use Committee (IACUC) of the Seoul National University (Protocol Number: SNU-150512-1-3). Experiments were conducted in accordance with guideline set by the Committee.

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Copyright information

© The Genetics Society of Korea 2019

Authors and Affiliations

  1. 1.Department of Laboratory Animal Medicine, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary MedicineSeoul National UniversitySeoulRepublic of Korea
  2. 2.Department of Stem Cell Biology, School of MedicineKonkuk UniversitySeoulRepublic of Korea
  3. 3.Department of Biochemistry, College of Life Sctalenience and Biotechnology and Yonsei Laboratory Animal Research CenterYonsei UniversitySeoulRepublic of Korea

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