Mice with a homozygous gene trap vector insertion in mgcRacGAP die during pre-implantation development.
Mech Dev
; 102(1-2): 33-44, 2001 Apr.
Article
in En
| MEDLINE
| ID: mdl-11287179
ABSTRACT
In a phenotypic screen in mice using a gene trap approach in embryonic stem cells, we have identified a recessive loss-of-function mutation in the mgcRacGAP gene. Maternal protein is present in the oocyte, and mgcRacGAP gene transcription starts at the four-cell stage and persists throughout mouse pre-implantation development. Total mgcRacGAP deficiency results in pre-implantation lethality. Such E3.5 embryos display a dramatic reduction in cell number, but undergo compaction and form a blastocoel. At E3.0-3.5, binucleated blastomeres in which the nuclei are partially interconnected are frequently observed, suggesting that mgcRacGAP is required for normal mitosis and cytokinesis in the pre-implantation embryo. All homozygous mutant blastocysts fail to grow out on fibronectin-coated substrates, but a fraction of them can still induce decidual swelling in vivo. The mgcRacGAP mRNA expression pattern in post-implantation embryos and adult mouse brain suggests a role in neuronal cells. Our results indicate that mgcRacGAP is essential for the earliest stages of mouse embryogenesis, and add evidence that CYK-4-like proteins also play a role in microtubule-dependent steps in the cytokinesis of vertebrate cells. In addition, the severe phenotype of null embryos indicates that mgcRacGAP is functionally non-redundant and cannot be substituted by other GAPs during early cleavage of the mammalian embryo.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription, Genetic
/
GTPase-Activating Proteins
/
GTP Phosphohydrolase Activators
/
Embryo, Mammalian
/
Homozygote
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Mech Dev
Journal subject:
EMBRIOLOGIA
Year:
2001
Document type:
Article
Affiliation country:
Bélgica