HUMAN RED-CELL AQUAPORIN CHIP .2. EXPRESSION DURING NORMAL FETAL DEVELOPMENT AND IN A NOVEL FORM OF CONGENITAL DYSERYTHROPOIETIC ANEMIA

Channel-forming integral protein (CHIP) is the archetypal member of th e Aquaporin family of water channels. Delayed CHIP expression was show n recently in perinatal rat (Smith, B. L., R. Baumgarten, S. Nielsen, D. Raben, M. L. Zeidel, and P. Agre. 1993. J. Clin. Invest. 92:2035-20 41); here we delineate the human patterns. Compared with adult, second and third trimester human fetal red cells had lower CHIP/spectrin rat ios (0.72+/-0.12, 0.94+/-0.22 vs 1.18+/-0.11) and reduced osmotic wate r permeability (0.029, 0.026 vs 0.037 cm/s); CHIP was already present in human renal tubules by the second trimester. A patient with a novel form of congenital dyserythropoietic anemia (CDA) with persistent emb ryonic and fetal globins and absent red cell CD44 protein was studied because of reduced CHIP-associated Colton antigens. Novel CDA red cell s contained < 10% of the normal level of CHIP and had remarkably low o smotic water permeability (< 0.01 cm/s), but no mutation was identifie d in Aquaporin-1, the gene encoding CHIP. These studies demonstrate: ( a) unlike rat, human CHIP expression occurs early in fetal development ; (b) red cell water channels are greatly reduced in a rare phenotype; and (c) disrupted expression of red cell CHIP and CD44 suggests an ap proach to the molecular defect in a novel form of CDA.