title: Sleeping beauty transposon-based phenotypic analysis of mice: lack of Arpc3 results in defective trophoblast outgrowth.
abstract: The Sleeping Beauty (SB) transposon system has generated many transposon-insertional mutant mouse lines, some of which have resulted in embryonic lethality when bred to homozygosity. Here we report one such insertion mapped to the mouse actin-related protein complex subunit 3 gene (Arpc3). Arpc3 is a component of the Arp2/3 complex, which plays a major role in actin nucleation with Y-shaped branching from the mother actin filament in response to migration signaling. Arpc3 transposon-inserted mutants developed only to the blastocyst stage. In vitro blastocyst culture of Arpc3 mutants exhibited severe spreading impairment of trophoblasts. This phenotype was also observed in compound heterozygotes generated using conventional gene-targeted and transposon-inserted alleles. Arpc3-deficient mutants were shown to lack actin-rich structures in the spreading trophoblast. Electron microscopic analysis demonstrated the lack of mesh-like structures at the cell periphery, suggesting a role of Arpc3 in Y-shaped branching formation. These data indicate the importance of Arpc3 in the Arp2/3 complex for trophoblast outgrowth and suggest that Arpc3 may be indispensable for implantation.
authors.affiliation: Department of Social and Environmental Medicine H3, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Kojiro
authors.initials: K
authors.lastname: Yae
authors.forename: Vincent W
authors.initials: VW
authors.lastname: Keng
authors.forename: Masato
authors.initials: M
authors.lastname: Koike
authors.forename: Kosuke
authors.initials: K
authors.lastname: Yusa
authors.forename: Michiyoshi
authors.initials: M
authors.lastname: Kouno
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Uno
authors.forename: Gen
authors.initials: G
authors.lastname: Kondoh
authors.forename: Takahiro
authors.initials: T
authors.lastname: Gotow
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Uchiyama
authors.forename: Kyoji
authors.initials: K
authors.lastname: Horie
authors.forename: Junji
authors.initials: J
authors.lastname: Takeda
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000172:deficiency*; D000199:Actins / Q000378:metabolism; D000818:Animals; D033481:Chromosomes, Mammalian / Q000235:genetics; D003599:Cytoskeleton / Q000648:ultrastructure; D004251:DNA Transposable Elements / Q000235:genetics; D005816:Genetic Complementation Test; D007438:Introns / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016254:Mutagenesis, Insertional; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D019895:Transposases / Q000235:genetics*; D014327:Trophoblasts / Q000166:cytology / Q000473:pathology* / Q000648:ultrastructure
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; C513333:Arpc3 protein, mouse; D004251:DNA Transposable Elements; D019895:Transposases