title: AQP3 deficiency in humans and the molecular basis of a novel blood group system, GIL.
abstract: AQP3 is a water and glycerol channel present on human erythrocytes and in various tissues. By protein and molecular biology analysis, two unrelated probands who developed alloantibodies to the high frequency antigen GIL were found to be AQP3-deficient. The defect is caused by homozygous mutation affecting the 5' donor splice site of intron 5 of the AQP3 gene. This mutation causes the skipping of exon 5 and generates a frameshift and premature stop codon. Functional studies by 90 degrees light scattering using a stopped-flow spectrometer revealed the absence of facilitated glycerol transport across red cell membranes from the probands, but the water and urea transports were normal. Expression studies into COS-7 cells followed by flow cytometry analysis showed that only cells transfected with AQP3 cDNA strongly reacted with anti-GIL antibodies. These findings represent the first reported cases of AQP3 deficiency in humans and provide the molecular basis of a new blood group system, GIL, encoded by the AQP3 protein.
authors.affiliation: INSERM U76, Institut National de la Transfusion Sanguine, 6 rue Alexandre Cabanel, 75015 Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Roudier
authors.forename: Pierre
authors.initials: P
authors.lastname: Ripoche
authors.forename: Pierre
authors.initials: P
authors.lastname: Gane
authors.forename: Pierre Yves
authors.initials: PY
authors.lastname: Le Pennec
authors.forename: Geoff
authors.initials: G
authors.lastname: Daniels
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cartron
authors.forename: Pascal
authors.initials: P
authors.lastname: Bailly
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D051400:Aquaporin 3; D020346:Aquaporins / Q000737:chemistry / Q000235:genetics*; D001789:Blood Group Antigens / Q000235:genetics*; D019556:COS Cells; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D017386:Sequence Homology, Amino Acid
chemical_list: C496027:AQP3 protein, human; D020346:Aquaporins; D001789:Blood Group Antigens; D051400:Aquaporin 3; D005990:Glycerol