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Title: Mice with a homozygous gene trap vector insertion in mgcRacGAP die during pre-implantation development
Authors: Van de Putte, Tom ×
Zwijsen, An
Lonnoy, Olivier
Rybin, V
Cozijnsen, M
Francis, Annick
Baekelandt, Veerle
Kozak, C A
Zerial, M
Huylebroeck, Danny #
Issue Date: Apr-2001
Publisher: Elsevier Scientific Publishers Ireland
Series Title: Mechanisms of Development vol:102 issue:1-2 pages:33-44
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.
ISSN: 0925-4773
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Research Group for Neurobiology and Gene Therapy
Molecular Biology (Celgen) (-)
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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