Connexin 43 Contributes to Phenotypic Variability of the Mouse Skull
Abstract
The purpose of this study was to determine whether connexin 43 (Cx43) contributes to craniofacial phenotypic variability. Skull shape and variation were compared within and among two heterozygous mutant mouse models (G60S/+ and I130T/+) that exhibit different levels of Cx43 channel function when compared to their wildtype counterparts (~80% and ~50% reduction in function, respectively). Results indicated mutants have significant differences in skull shape compared to wildtype littermates. Similar patterns of shape difference were found in both mutants. Increased skull shape variation and a disruption in the covariation of skull structures were observed in G60S/+ mutants only. These results show that while a 50% reduction in Cx43 function causes a shift in mean skull shape, there is a lower threshold at which Cx43 function disrupts craniofacial phenotypic robustness. This study demonstrates that Cx43 can contribute to phenotypic variability of the skull through a nonlinear relationship between Cx43 function and phenotypic outcomes.