eLife (May 2021)
Disruption of entire Cables2 locus leads to embryonic lethality by diminished Rps21 gene expression and enhanced p53 pathway
- Tra Thi Huong Dinh,
- Hiroyoshi Iseki,
- Seiya Mizuno,
- Saori Iijima-Mizuno,
- Yoko Tanimoto,
- Yoko Daitoku,
- Kanako Kato,
- Yuko Hamada,
- Ammar Shaker Hamed Hasan,
- Hayate Suzuki,
- Kazuya Murata,
- Masafumi Muratani,
- Masatsugu Ema,
- Jun-Dal Kim,
- Junji Ishida,
- Akiyoshi Fukamizu,
- Mitsuyasu Kato,
- Satoru Takahashi,
- Ken-ichi Yagami,
- Valerie Wilson,
- Ruth M Arkell,
- Fumihiro Sugiyama
Affiliations
- Tra Thi Huong Dinh
- ORCiD
- Laboratory Animal Resource Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan; Ph.D. Program in Human Biology, School of Integrative and Global Majors (SIGMA), University of Tsukuba, Tsukuba, Japan; Department of Traditional Medicine, University of Medicine and Pharmacy, Ho Chi Minh City, Viet Nam; Transborder Medical Research Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
- Hiroyoshi Iseki
- ORCiD
- Laboratory Animal Resource Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan
- Seiya Mizuno
- ORCiD
- Laboratory Animal Resource Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan; Transborder Medical Research Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
- Saori Iijima-Mizuno
- Laboratory Animal Resource Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan; Experimental Animal Division, RIKEN BioResource Research Center, Tsukuba, Japan
- Yoko Tanimoto
- ORCiD
- Laboratory Animal Resource Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
- Yoko Daitoku
- Laboratory Animal Resource Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
- Kanako Kato
- Laboratory Animal Resource Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
- Yuko Hamada
- Laboratory Animal Resource Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
- Ammar Shaker Hamed Hasan
- Laboratory Animal Resource Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan; Doctor’s Program in Biomedical Sciences, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan
- Hayate Suzuki
- Laboratory Animal Resource Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan; Doctor’s Program in Biomedical Sciences, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan
- Kazuya Murata
- ORCiD
- Laboratory Animal Resource Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan; Transborder Medical Research Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
- Masafumi Muratani
- Transborder Medical Research Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan; Department of Genome Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
- Masatsugu Ema
- ORCiD
- Department of Stem Cells and Human Disease Models, Research Center for Animal Life Science, Shiga University of Medical Science, Otsu, Japan; Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, Japan
- Jun-Dal Kim
- ORCiD
- Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba, Japan; Division of Complex Bioscience Research, Department of Research and Development, Institute of National Medicine, University of Toyama, Toyama, Japan
- Junji Ishida
- ORCiD
- Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba, Japan
- Akiyoshi Fukamizu
- ORCiD
- Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba, Japan
- Mitsuyasu Kato
- ORCiD
- Transborder Medical Research Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan; Department of Experimental Pathology, Faculty of. Medicine, University of Tsukuba, Tsukuba, Japan
- Satoru Takahashi
- ORCiD
- Laboratory Animal Resource Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan; Transborder Medical Research Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
- Ken-ichi Yagami
- Laboratory Animal Resource Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
- Valerie Wilson
- ORCiD
- MRC Centre for Regenerative Medicine, School of Biological Sciences, SCRM Building, The University of Edinburgh, Edinburgh, United Kingdom
- Ruth M Arkell
- ORCiD
- John Curtin School of Medical Research, The Australian National University, Canberra, Australia
- Fumihiro Sugiyama
- ORCiD
- Laboratory Animal Resource Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan; Transborder Medical Research Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
- DOI
- https://doi.org/10.7554/eLife.50346
- Journal volume & issue
-
Vol. 10
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.
Keywords
