Optometry Research Today is a free monthly online journal that collates and summarizes the latest research about Optometry, including details on myopia, optometric practice, therapy.

Knock-in of alpha3 connexin prevents severe cataracts caused by an alpha8 point mutation.

Xia CH, Cheung D, DeRosa AM, Chang B, Lo WK, White TW, Gong X

School of Optometry and Vision Science Program, University of California at Berkeley, Berkeley, CA, USA.

A G22R point mutation in alpha8 connexin (Cx50) has been previously shown to cause a severe cataract by interacting with endogenous wild-type alpha3 connexin (Cx46) in mouse lenses. Here, we tested whether a knocked-in alpha3 connexin expressed on the locus of the endogenous alpha8 connexin could modulate the severe cataract caused by the alpha8-G22R mutation. We found that the alpha3(-/-) alpha8(G22R/-) mice developed severe cataracts with disrupted inner fibers and posterior rupture while the alpha3(-/-) alpha8(G22R/KIalpha3) lens contained relatively normal inner fibers without lens posterior rupture. The alpha8-G22R mutant proteins produced typical punctate staining of gap junctions between fiber cells of alpha3(-/-) alpha8(G22R/KIalpha3) lenses, but not in those of alpha3(-/-) alpha8(G22R/-) lenses. Thus, we hypothesize that the knocked-in alpha3 connexin subunits interact with the alpha8-G22R connexin subunits to form functional gap junction channels and rescue the lens phenotype. Using an electrical coupling assay consisting of paired Xenopus oocytes, we demonstrated that only co-expression of mutant alpha8-G22R and wild-type alpha3 connexin subunits forms functional gap junction channels with reduced conductance and altered voltage sensitivity compared with the channels formed by alpha3 connexin subunits alone. Thus, knocked-in alpha3 connexin and mutant alpha8-G22R connexin probably form heteromeric gap junction channels that influence lens homeostasis and lens transparency.

Published 11 May 2006 in J Cell Sci, 119: 2138-44.
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