Levels and Modifications of Both Lens Fiber Cell Connexins Are Affected in Connexin Mutant Mice

In the lens, cell homeostasis and transparency are supported by intercellular communication facilitated by the channels formed of connexin46 (Cx46) and connexin50 (Cx50). Mutations of these connexins are linked to inherited cataracts. We studied the levels and the variations in electrophoretic mobilities of the immunoreactive Cx46 and Cx50 bands between 1 and 21 days after birth in the lenses of wild-type mice and homozygous animals from two different mouse models of connexin-linked cataracts (Cx46fs380 and Cx50D47A). In Cx50D47A mice, the expression of the mutant Cx50 reduced the normal phosphorylation of the co-expressed wild-type Cx46. In both models, levels of the mutant connexin and the co-expressed wild-type connexin decayed more rapidly than in wild-type mice but with different time courses. In the Cx46fs380 mice, modeling suggested that Cx50 degradation could be explained by the mixing of mutant Cx46 with wild-type Cx50. However, in Cx50D47A mice, similar modeling suggested that mixing alone could not explain the decrease in Cx46 levels. These data highlight the complex influences between two connexin proteins expressed in the same cell, some of which occur through direct mixing, while others occur indirectly, as in Cx50D47A mice, where the expression of the mutant connexin causes endoplasmic reticulum stress and impaired differentiation.