Defective Urinary Concentrating Ability Due to a Complete Deficiency of Aquaporin-1
Carlton, J P
Fernandez, P C
King, L S
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Aquaporin-1, the archetypal water-channel protein,1 was initially identified in red cells and renal proximal tubular epithelium.2 The gene for aquaporin-1 (AQP1) on chromosome 7 colocalizes with the Colton blood-group antigen,3,4 and the Colton blood-group antigen polymorphism was identified as a substitution of a single amino acid in an extracellular domain of aquaporin-1.5 The International Blood Group Reference Laboratory has confirmed the existence of only six kindreds who lack the Colton blood group. Members of three of these kindreds were found to be homozygous for different mutations in the AQP1 gene, and their red-cell membranes had a complete absence or a marked reduction of aquaporin-1.6,7 Surprisingly, aquaporin-1 deficiency had no obvious clinical consequence in these people. Since aquaporin-1 is abundant in renal proximal tubular epithelium, the thin descending limb of the loop of Henle, and the descending vasa recta of the kidney,8,9 we hypothesized that people with a deficiency of aquaporin-1 have defects in water homeostasis in the kidneys that can be identified only under conditions of stress. We studied two unrelated subjects with a deficiency of aquaporin-1 and found that they had impaired urinary concentrating ability, suggesting that aquaporin-1 has a physiologic role in renal function.