MUTATIONS IN AQUAPORIN-1 IN PHENOTYPICALLY NORMAL HUMANS WITHOUT FUNCTIONAL CHIP WATER CHANNELS

The gene aquaporin-1 encodes channel-forming integral protein (CHIP), a member of a large family of water transporters found throughout natu re. Three rare individuals were identified who do not express CHIP-ass ociated Colton blood group antigens and whose red cells exhibit low os motic water permeabilities. Genomic DNA analyses demonstrated that two individuals were homozygous for different nonsense mutations (exon de letion or frameshift), and the third had a missense mutation encoding a nonfunctioning CHIP molecule. Surprisingly, none of the three suffer s any apparent clinical consequence, which raises questions about the physiologicai importance of CHIP and implies that other mechanisms may compensate for its absence.