Absence of alpha3 (Cx46) and alpha8 (Cx50) connexins leads to cataracts by affecting lens inner fiber cells.
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.
Xia
Chun-hong
CH
School of Optometry and Vision Science Program, University of California at Berkeley, 693 Minor Hall, Berkeley, CA 94720-2020, USA.
Cheng
Catherine
C
Huang
Qingling
Q
Cheung
Debra
D
Li
Lin
L
Dunia
Irene
I
Benedetti
Lucio E
LE
Horwitz
Joseph
J
Gong
Xiaohua
X
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
D017630:Connexins; D005136:Eye Proteins; D038222:gamma-Crystallins; D000099264:Connexin 50; C082917:GJA3 protein, human