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 nature. Three rare individuals were identified who do not express CHIP-associated Colton blood group antigens and whose red cells exhibit low osmotic water permeabilities. Genomic DNA analyses demonstrated that two individuals were homozygous for different nonsense mutations (exon deletion or frameshift), and the third had a missense mutation encoding a nonfunctioning CHIP molecule. Surprisingly, none of the three suffers any apparent clinical consequence, which raises questions about the physiological importance of CHIP and implies that other mechanisms may compensate for its absence.
Preston
G M
GM
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Smith
B L
BL
Zeidel
M L
ML
Moulds
J J
JJ
Agre
P
P
D000818:Animals; D051398:Aquaporin 1; D020346:Aquaporins; D001483:Base Sequence; D001789:Blood Group Antigens; D002463:Cell Membrane Permeability; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000502:physiology; D005091:Exons; D005260:Female; D006720:Homozygote; D006801:Humans; D007473:Ion Channels / Q000097:blood / Q000235:genetics* / Q000652:urine; D007684:Kidney Tubules / Q000737:chemistry; D008969:Molecular Sequence Data; D009154:Mutation; D009865:Oocytes; D010641:Phenotype; D016133:Polymerase Chain Reaction; D014981:Xenopus
C496020:AQP1 protein, human; D020346:Aquaporins; D001789:Blood Group Antigens; D007473:Ion Channels; D051398:Aquaporin 1