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

doi:10.7554/eLife.50346

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 WilsonRuth M. Arkell, Fumihiro Sugiyama^*

^*Corresponding author for this work

Complex Biosystem Research, Institute of Natural Medicine

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

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.

Original language	English
Article number	e50346
Journal	eLife
Volume	10
DOIs	https://doi.org/10.7554/eLife.50346
State	Published - 2021/05

ASJC Scopus subject areas

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

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Dinh, T. T. H., Iseki, H., Mizuno, S., Iijima-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. I., ... Sugiyama, F. (2021). Disruption of entire Cables2 locus leads to embryonic lethality by diminished Rps21 gene expression and enhanced p53 pathway. eLife, 10, Article e50346. https://doi.org/10.7554/eLife.50346

@article{60a8d37967b04bcd8314e0bfebdbf410,

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

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.",

author = "Dinh, {Tra Thi Huong} and Hiroyoshi Iseki and Seiya Mizuno and Saori Iijima-Mizuno and Yoko Tanimoto and Yoko Daitoku and Kanako Kato and Yuko Hamada and Hasan, {Ammar Shaker Hamed} and Hayate Suzuki and Kazuya Murata and Masafumi Muratani and Masatsugu Ema and Kim, {Jun Dal} and Junji Ishida and Akiyoshi Fukamizu and Mitsuyasu Kato and Satoru Takahashi and Yagami, {Ken ichi} and Valerie Wilson and Arkell, {Ruth M.} and Fumihiro Sugiyama",

note = "Publisher Copyright: {\textcopyright} Dinh et al.",

year = "2021",

month = may,

doi = "10.7554/eLife.50346",

language = "英語",

volume = "10",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications Ltd",

}

Dinh, TTH, Iseki, H, Mizuno, S, Iijima-Mizuno, S, Tanimoto, Y, Daitoku, Y, Kato, K, Hamada, Y, Hasan, ASH, Suzuki, H, Murata, K, Muratani, M, Ema, M, Kim, JD, Ishida, J, Fukamizu, A, Kato, M, Takahashi, S, Yagami, KI, Wilson, V, Arkell, RM & 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

TY - JOUR

T1 - Disruption of entire Cables2 locus leads to embryonic lethality by diminished Rps21 gene expression and enhanced p53 pathway

AU - Dinh, Tra Thi Huong

AU - Iseki, Hiroyoshi

AU - Mizuno, Seiya

AU - Iijima-Mizuno, Saori

AU - Tanimoto, Yoko

AU - Daitoku, Yoko

AU - Kato, Kanako

AU - Hamada, Yuko

AU - Hasan, Ammar Shaker Hamed

AU - Suzuki, Hayate

AU - Murata, Kazuya

AU - Muratani, Masafumi

AU - Ema, Masatsugu

AU - Kim, Jun Dal

AU - Ishida, Junji

AU - Fukamizu, Akiyoshi

AU - Kato, Mitsuyasu

AU - Takahashi, Satoru

AU - Yagami, Ken ichi

AU - Wilson, Valerie

AU - Arkell, Ruth M.

AU - Sugiyama, Fumihiro

PY - 2021/5

Y1 - 2021/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85105494480&partnerID=8YFLogxK

U2 - 10.7554/eLife.50346

DO - 10.7554/eLife.50346

M3 - 学術論文

C2 - 33949947

AN - SCOPUS:85105494480

SN - 2050-084X

VL - 10

JO - eLife

JF - eLife

M1 - e50346

ER -

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

Abstract

ASJC Scopus subject areas

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