In order to investigate the potential roles of Forkhead Box c2（Fox c2）in cardiovascular development, mice lacking Fox c2 locus were produced by targeted mutation and the developmental anomalies in the aortic arch were found. Mice homozygotes for the mutation(Fox c2^－/－) died embryonically from E12.5 (embryo days, E) to term. Although some of the homozygous mutants were born with abnormalities of the aortic arch, all of them died within 24 h after birth. Fox c2^－/－ homozygous mutants all displayed the Type B or Type C of interrupted aortic arch, which is the same as human congenital cardiovascular anomalies. Mice heterozygous for the mutation developed normally. In situ hybridization analysis on E10.5 embryos showed that Fox c2 mRNA expressed at the third, fourth and sixth arch arteries strongly. However, left fourth arch arteries disappeared at E12.5 gradually. These results suggest that the Fox c2 plays indispensable role in the remodeling of left fourth arch arteries during the formation of aortic arch.