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1 Departments of Ophthalmology and Visual Sciences
2 Genetics
3 Cell Biology Washington University School of Medicine, St. Louis, Missouri 63110
4 Department of Physiology, State University of New York, Stony Brook, New York 11794
5 Departments of Anatomy
6 Pathology
7 Ophthalmology, Rush-Presbyterian-St. Luke’s Medical Center, Chicago, Illinois 60612
8 Lexicon Genetics, The Woodlands, Texas 77381
Aquaporin-0 (AQP0), a water transport channel protein, is the major intrinsic protein (MIP) of lens fiber cell plasma membranes. Mice deficient in the gene for AQP0 (Aqp0, Mip) were generated from a library of gene trap embryo stem cells. Sequence analysis showed that the gene trap vector had inserted into the first exon of Aqp0, causing a null mutation as verified by RNA blotting and immunochemistry. At 3 wk of age (postnatal day 21), lenses from null mice (Aqp0-/-) contained polymorphic opacities, whereas lenses from heterozygous mice (Aqp0+/-) were transparent and did not develop frank opacities until 
24 wk of age. Osmotic water permeability values for Aqp0+/- and Aqp0-/- lenses were reduced to 46% and 20% of wild-type values, respectively, and the focusing power of Aqp0+/- lenses was significantly lower than that of wild type. These findings show that heterozygous loss of AQP0 is sufficient to trigger cataractogenesis in mice and suggest that this MIP is required for optimal focusing of the crystalline lens.
cataract; gene trap; mouse; water channel
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