Disruption of entire Cables2 locus leads to embryonic lethality by diminished Rps21 gene expression and enhanced p53 pathway-Reference-Cited by-同舟云学术

Disruption of entire Cables2 locus leads to embryonic lethality by diminished Rps21 gene expression and enhanced p53 pathway

Published:2021-05-05 Issue: Volume:10 Page:
ISSN:2050-084X
Container-title:eLife
language:en
Short-container-title:

Author:

Dinh Tra Thi Huong¹²³⁴^ORCID,Iseki Hiroyoshi¹⁵^ORCID,Mizuno Seiya¹⁴^ORCID,Iijima-Mizuno Saori¹⁶,Tanimoto Yoko¹^ORCID,Daitoku Yoko¹,Kato Kanako¹,Hamada Yuko¹,Hasan Ammar Shaker Hamed¹⁷,Suzuki Hayate¹⁷,Murata Kazuya¹⁴^ORCID,Muratani Masafumi⁴⁸,Ema Masatsugu⁹¹⁰^ORCID,Kim Jun-Dal¹¹¹²^ORCID,Ishida Junji¹¹^ORCID,Fukamizu Akiyoshi¹¹^ORCID,Kato Mitsuyasu⁴¹³^ORCID,Takahashi Satoru¹⁴^ORCID,Yagami Ken-ichi¹,Wilson Valerie¹⁴^ORCID,Arkell Ruth M¹⁵^ORCID,Sugiyama Fumihiro¹⁴^ORCID

Affiliation:

1. Laboratory Animal Resource Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

2. Ph.D. Program in Human Biology, School of Integrative and Global Majors (SIGMA), University of Tsukuba, Tsukuba, Japan

3. Department of Traditional Medicine, University of Medicine and Pharmacy, Ho Chi Minh City, Viet Nam

4. Transborder Medical Research Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

5. International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan

6. Experimental Animal Division, RIKEN BioResource Research Center, Tsukuba, Japan

7. Doctor’s Program in Biomedical Sciences, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan

8. Department of Genome Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

9. Department of Stem Cells and Human Disease Models, Research Center for Animal Life Science, Shiga University of Medical Science, Otsu, Japan

10. Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, Japan

11. Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba, Japan

12. Division of Complex Bioscience Research, Department of Research and Development, Institute of National Medicine, University of Toyama, Toyama, Japan

13. Department of Experimental Pathology, Faculty of. Medicine, University of Tsukuba, Tsukuba, Japan

14. MRC Centre for Regenerative Medicine, School of Biological Sciences, SCRM Building, The University of Edinburgh, Edinburgh, United Kingdom

15. John Curtin School of Medical Research, The Australian National University, Canberra, Australia

Abstract

In vivo function of CDK5 and Abl enzyme substrate 2 (Cables2), belonging to the Cables protein family, is unknown. Here, we found that targeted disruption of the entire Cables2 locus (Cables2d) caused growth retardation and enhanced apoptosis at the gastrulation stage and then induced embryonic lethality in mice. Comparative transcriptome analysis revealed disruption of Cables2, 50% down-regulation of Rps21 abutting on the Cables2 locus, and up-regulation of p53-target genes in Cables2d gastrulas. We further revealed the lethality phenotype in Rps21-deleted mice and unexpectedly, the exon 1-deleted Cables2 mice survived. Interestingly, chimeric mice derived from Cables2d ESCs carrying exogenous Cables2 and tetraploid wild-type embryo overcame gastrulation. These results suggest that the diminished expression of Rps21 and the completed lack of Cables2 expression are intricately involved in the embryonic lethality via the p53 pathway. This study sheds light on the importance of Cables2 locus in mouse embryonic development.

Funder

Grant-in-Aid for Scientific Research(B), Japan Society for the Promotion of Science

Grant-in-Aid for Scientific Research(S), Japan Society for the Promotion of Science

Grant-in-Aid for Scientific Research(C), Japan Society for the Promotion of Science

Grant-in-Aid for Young Scientists (B), Japan Society for the Promotion of Science

Grant-in-Aid for Scientific Research(A), Japan Society for the Promotion of Science

The Cooperative Research Project Program of Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA Center), University of Tsukuba, Japan

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Link

https://cdn.elifesciences.org/articles/50346/elife-50346-v1.pdf

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