Sleeping beauty transposon-based phenotypic analysis of mice: lack of Arpc3 results in defective trophoblast outgrowth.
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.
Yae
Kojiro
K
Department of Social and Environmental Medicine H3, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Keng
Vincent W
VW
Koike
Masato
M
Yusa
Kosuke
K
Kouno
Michiyoshi
M
Uno
Yoshihiro
Y
Kondoh
Gen
G
Gotow
Takahiro
T
Uchiyama
Yasuo
Y
Horie
Kyoji
K
Takeda
Junji
J
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
D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; C513333:Arpc3 protein, mouse; D004251:DNA Transposable Elements; D019895:Transposases