Roles of the Foxj1 and Inv genes in the left–right determination of internal organs in mice

In Foxj1 knockout mice, half show situs solitus while the other half show situs inversus, which means a random determination of the left–right axis. In contrast, the inv mutant mice show a mirror-image configuration of the internal organs, which means a reversal of the left–right axis. Although these two mutant mice have primary cilia on the nodal cells, their phenotypes are different in laterality determination. We thus made Foxj1/inv double mutant mice and analyzed their phenotype. We found the phenotypes of Foxj1/inv double mutant mice to be more similar to those of the Foxj1 mutant mice than those of the inv mutant mice. We also found right pulmonary isomerism to be a major phenotype of the Foxj1 mutant mice and the Foxj1/inv double mutant mice, which is likely due to the absence of the Pitx2 expression at both lateral plate mesoderms. These results indicate that a random signal of laterality (Foxj1) is dominant over the reversal signal of laterality (Inv).