title: Fliih, a gelsolin-related cytoskeletal regulator essential for early mammalian embryonic development.
abstract: 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 FLII gene and shown that the FLII 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.
authors.affiliation: Molecular Genetics and Evolution Group, Research School of Biological Sciences, Australian National University, Canberra, ACT 2601, Australia. Hugh.Campbell@anu.edu.au
authors.forename: Hugh D
authors.initials: HD
authors.lastname: Campbell
authors.forename: Shelley
authors.initials: S
authors.lastname: Fountain
authors.forename: Ian S
authors.initials: IS
authors.lastname: McLennan
authors.forename: Leise A
authors.initials: LA
authors.lastname: Berven
authors.forename: Michael F
authors.initials: MF
authors.lastname: Crouch
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Davy
authors.forename: Jane A
authors.initials: JA
authors.lastname: Hooper
authors.forename: Kynan
authors.initials: K
authors.lastname: Waterford
authors.forename: Ken-Shiung
authors.initials: KS
authors.lastname: Chen
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
authors.forename: Birgit
authors.initials: B
authors.lastname: Ledermann
authors.forename: Ian G
authors.initials: IG
authors.lastname: Young
authors.forename: Klaus I
authors.initials: KI
authors.lastname: Matthaei
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000378:metabolism*; D029721:Drosophila Proteins; D010064:Embryo Implantation; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology*; D005260:Female; D018260:Gelsolin; D018390:Gene Targeting; D006801:Humans; D019476:Insect Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008840:Microfilament Proteins; D011247:Pregnancy; D011506:Proteins / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D015534:Trans-Activators; D014599:Uterus / Q000166:cytology
chemical_list: D000199:Actins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; C000609263:FlII protein, mouse; D018260:Gelsolin; D019476:Insect Proteins; D008840:Microfilament Proteins; D011506:Proteins; D015534:Trans-Activators; C098178:fliI protein, Drosophila