Purchase this article with an account.
F.J. Martinez–Wittinghan, C. Sellitto, T.W. White, R.T. Mathias; Partial Phenotype Rescue in Mice Lacking Cx50 by Knock Over of Cx46 . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1850.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Lens connexin knockout (KO) and knockin (KI) mice have provided evidence that Cx50 is required for normal lens growth whereas Cx46 is needed for coupling of the central core of mature fibers (MF). To further test these hypotheses, we studied the coupling and gating characteristics of lenses from knockover mice (KI mice where the native Cx46 gene has been knocked out, i.e. Cx46(–/–) Cx50(46/46)). Methods: Mouse lenses (4–6 weeks old) were dissected and gap junction coupling was evaluated using the whole lens impedance technique. To assess the response to acidification, the bath solution was bubbled with 100% CO2. Results: Knockover lenses were smaller than wild type (diameter was 88±0.004% of normal) but they did not have a cataract. The coupling conductances below are normalized to the value in the outer shell of differentiating fibers (DF) of WT lenses: GDF WT=1, n = 20, knockover = 0.43±0.03 , n = 8; GMF WT = 0.53±0.02, n = 25, knockover = 1.59±0.28 , n = 8). The pH sensitivity of knockover lenses was similar to that of WT. Conclusions: Knocking over Cx46 to the Cx50 locus restores clarity but not size, however, this recovery is not directly related to coupling conductance of DF, since GDF of knockover lenses was reduced to similar levels as those reported for the Cx50 KO (∼40% of wild type). On the other hand, the coupling conductance of MF in the knockover lenses was increased above the value for WT. Thus, the recovery from the cataract phenotype appeared to be achieved by the increased (or maintained) conductance in the MF. These findings are consistent with our hypotheses on the roles of these connexins. However, the mechanism for the increase in GMF is not understood. It may involve posttranslational modifications at the DF to MF transition, but these appear to only be made to Cx46 only when it is expressed from the Cx50 gene locus.
This PDF is available to Subscribers Only