Back to Search
Start Over
Disruption of entire Cables2 locus leads to embryonic lethality by diminished Rps21 gene expression and enhanced p53 pathway
- Source :
- eLife, Vol 10 (2021), Dinh, T T H, Iseki, H, Mizuno, S, Lijima-Mizuno, S, Tanimoto, Y, Daitoku, Y, Kato, K, Hamada, Y, Hasan, A S H, Suzuki, H, Murata, K, Muratani, M, Ema, M, Kim, J-D, Ishida, J, Fukamizu, A, Kato, M, Takahashi, S, Yagami, K, Wilson, V, Arkell, R M & Sugiyama, F 2021, ' Disruption of entire Cables2 locus leads to embryonic lethality by diminished Rps21 gene expression and enhanced p53 pathway ', eLIFE, vol. 10, e50346 . https://doi.org/10.7554/eLife.50346
- Publication Year :
- 2021
- Publisher :
- eLife Sciences Publications Ltd, 2021.
-
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 entireCables2locus (Cables2d) caused growth retardation and enhanced apoptosis at the gastrulation stage and then induced embryonic lethality in mice. Comparative transcriptome analysis revealed disruption ofCables2, 50% down-regulation ofRps21abutting on theCables2locus, and up-regulation of p53-target genes inCables2dgastrulas. We further revealed the lethality phenotype inRps21-deleted mice and unexpectedly, the exon 1-deletedCables2mice survived. Interestingly, chimeric mice derived fromCables2dESCs carrying exogenousCables2and tetraploid wild-type embryo overcame gastrulation. These results suggest that the diminished expression ofRps21and the completed lack ofCables2expression are intricately involved in the embryonic lethality via the p53 pathway. This study sheds light on the importance ofCables2locus in mouse embryonic development.
- Subjects :
- 0301 basic medicine
p53
QH301-705.5
Science
Locus (genetics)
Biology
cables2
Rps21
General Biochemistry, Genetics and Molecular Biology
Transcriptome
03 medical and health sciences
0302 clinical medicine
Gene expression
gastrulation
Biology (General)
General Immunology and Microbiology
embryonic lethality
General Neuroscience
Embryogenesis
Wnt/beta-catenin
Embryo
General Medicine
Phenotype
Embryonic stem cell
Cell biology
Gastrulation
030104 developmental biology
030220 oncology & carcinogenesis
Medicine
Subjects
Details
- Language :
- English
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- eLife
- Accession number :
- edsair.doi.dedup.....58aa969e49b4ef64147f91278c75d596