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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 …