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

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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.

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Abbreviations

KO:

Knockout

HR:

Homologous recombination

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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.

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Authors and Affiliations

  1. Department of Laboratory Animal Medicine, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea

    Ukjin Kim, Hanseul Oh, Ji Min Lee, Seo-Na Chang, Bokyeong Ryu, Jin Kim & Jae-Hak Park

  2. Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, 05029, Republic of Korea

    C-Yoon Kim

  3. Department of Biochemistry, College of Life Sctalenience and Biotechnology and Yonsei Laboratory Animal Research Center, Yonsei University, Seoul, 03722, Republic of Korea

    Han-Woong Lee

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  1. Ukjin Kim
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  3. Hanseul Oh
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  4. Ji Min Lee
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Correspondence to Jae-Hak Park.

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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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Kim, U., Kim, CY., Oh, H. et al. Phenotyping analysis of p53 knockout mice produced by gene editing and comparison with conventional p53 knockout mice. Genes Genom 41, 701–712 (2019). https://doi.org/10.1007/s13258-019-00785-y

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