title: Bilateral congenital cataracts result from a gain-of-function mutation in the gene for aquaporin-0 in mice.
abstract: Cataract Tohoku (Cat(Tohm)) is a dominant cataract mutation that leads to severe degeneration of lens fiber cells. Linkage analysis showed that the Cat(Tohm) mutation is located on mouse chromosome 10, close to the gene for aquaporin-0 (Aqp0), which encodes a membrane protein that is expressed specifically in lens fiber cells. Sequence analysis of Aqp0 revealed a 12-bp deletion without any change in the reading frame, which resulted in a deletion of four amino acids within the second transmembrane region of the AQP0 protein. Targeted expression of the mutated Aqp0 caused lens opacity in transgenic mice, the pathological severity of which depended on the expression level of the transgene. The mutated AQP0 protein was localized to the intracellular and perinuclear spaces rather than to the plasma membranes of the lens fiber cells. The cataract phenotype of Cat(Tohm) is caused by a gain-of-function mutation in the mutated AQP0 protein and not by a loss-of-function mutation.
authors.affiliation: Institute for Animal Experimentation, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Okamura
authors.forename: Ichiro
authors.initials: I
authors.lastname: Miyoshi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Mototani
authors.forename: Sadao
authors.initials: S
authors.lastname: Ishigaki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kon
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kasai
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020346:Aquaporins; D001483:Base Sequence; D015152:Blotting, Northern; D002386:Cataract / Q000151:congenital*; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D015870:Gene Expression; D007908:Lens, Crystalline / Q000033:anatomy & histology; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice / Q000033:anatomy & histology / Q000235:genetics*; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: D020346:Aquaporins; D005136:Eye Proteins; D008562:Membrane Glycoproteins; C030328:aquaporin 0