Fliih, a gelsolin-related cytoskeletal regulator essential for early mammalian embryonic development

被引:75
作者
Campbell, HD
Fountain, S
McLennan, IS
Berven, LA
Crouch, MF
Davy, DA
Hooper, JA
Waterford, K
Chen, KS
Lupski, JR
Ledermann, B
Young, IG
Matthaei, KI
机构
[1] Australian Natl Univ, Res Sch Biol Sci, Mol Genet & Evolut Grp, Canberra, ACT 2601, Australia
[2] Australian Natl Univ, John Curtin Sch Med Res, Div Biochem & Mol Biol, Canberra, ACT 2601, Australia
[3] GroPep Ltd, Thebarton, SA 5031, Australia
[4] Univ Otago, Dept Anat & Struct Biol, Dunedin, New Zealand
[5] Baylor Coll Med, Texas Med Ctr, Dept Mol & Human Genet, Houston, TX 77030 USA
[6] Univ Zurich Irchel, Inst Labortierkunde, CH-8057 Zurich, Switzerland
关键词
D O I
10.1128/MCB.22.10.3518-3526.2002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The Drosophila melanogaster flightless I gene is required for normal cellularization of the syncytial blastoderm. Highly conserved homologues of flightless I are present in Caenorhabditis elegans, mouse, and human. We have disrupted the mouse homologue Fliih by homologous recombination in embryonic stem cells. Heterozygous Fliih mutant mice develop normally, although the level of Fliih protein is reduced. Cultured homozygous Fliih mutant blastocysts hatch, attach, and form an outgrowing trophoblast cell layer, but egg cylinder formation fails and the embryos degenerate. Similarly, Fliih mutant embryos initiate implantation in vivo but then rapidly degenerate. We have constructed a transgenic mouse carrying the complete human FLIT gene and shown that the FLIT transgene is capable of rescuing the embryonic lethality of the homozygous targeted Fliih mutation. These results confirm the specific inactivation of the Fliih gene and establish that the human FLII gene and its gene product are functional in the mouse. The Fliih mouse mutant phenotype is much more severe than in the case of the related gelsolin family members gelsolin, villin, and CapG, where the homozygous mutant mice are viable and fertile but display alterations in cytoskeletal actin regulation.
引用
收藏
页码:3518 / 3526
页数:9
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