title: Absence of alpha3 (Cx46) and alpha8 (Cx50) connexins leads to cataracts by affecting lens inner fiber cells.
abstract: Lens development and transparency have been hypothesized to depend on intercellular gap junction channels, consisting of alpha3 (Cx46) and alpha8 (Cx50) connexin subunits, to transport metabolites, secondary messages and ions between lens cells. To evaluate this hypothesis, we have generated alpha3(-/-) alpha8(-/-) double knockout mice and characterized their lens phenotypes. Without gap junctions between lens fiber cells, alpha3(-/-) alpha8(-/-) lenses displayed severe cataracts resulting from cell swelling and degeneration of inner fibers while normal peripheral fiber cells continued to form throughout life. Neither an increase of degraded crystallins nor an increase of water-insoluble crystallins was found in alpha3(-/-) alpha8(-/-) lenses. However, a substantial reduction of gamma-crystallin proteins, but not alpha- and beta-crystallins, was detected. These results suggest that gap junction communication is important for maintaining lens homeostasis of inner fiber cells and that a loss of gap junctions leads to cataract formation as well as reductions of gamma-crystallin proteins and transcripts.
authors.affiliation: School of Optometry and Vision Science Program, University of California at Berkeley, 693 Minor Hall, Berkeley, CA 94720-2020, USA.
authors.forename: Chun-hong
authors.initials: CH
authors.lastname: Xia
authors.forename: Catherine
authors.initials: C
authors.lastname: Cheng
authors.forename: Qingling
authors.initials: Q
authors.lastname: Huang
authors.forename: Debra
authors.initials: D
authors.lastname: Cheung
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Irene
authors.initials: I
authors.lastname: Dunia
authors.forename: Lucio E
authors.initials: LE
authors.lastname: Benedetti
authors.forename: Joseph
authors.initials: J
authors.lastname: Horwitz
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Gong
mesh_terms: D000818:Animals; D002386:Cataract / Q000473:pathology*; D017630:Connexins / Q000235:genetics / Q000502:physiology*; D005136:Eye Proteins / Q000235:genetics / Q000502:physiology*; D005614:Freeze Fracturing; D017629:Gap Junctions / Q000473:pathology; D007908:Lens, Crystalline / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013194:Staining and Labeling; D038222:gamma-Crystallins / Q000235:genetics / Q000378:metabolism; D000099264:Connexin 50
chemical_list: D017630:Connexins; D005136:Eye Proteins; D038222:gamma-Crystallins; D000099264:Connexin 50; C082917:GJA3 protein, human