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Blood, 15 November 2008, Vol. 112, No. 10, pp. 4298-4307.
Prepublished online as a Blood First Edition Paper on August 22, 2008; DOI 10.1182/blood-2008-05-156000.
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RED CELLS
Targeted deletion of  -adducin results in absent β- and  -adducin, compensated hemolytic anemia, and lethal hydrocephalus in mice
Raymond F. Robledo1,
Steven L. Ciciotte1,
Babette Gwynn1,
Kenneth E. Sahr1,
Diana M. Gilligan2,
Narla Mohandas3, and
Luanne L. Peters1
1 The Jackson Laboratory, Bar Harbor, ME;
2 Puget Sound Blood Center, Seattle, WA; and
3 Red Cell Physiology Laboratory, New York Blood Center, New York, NY
In the red blood cell (RBC), adducin is present primarily as tetramers of  - and β-subunits at spectrin-actin junctions, or junctional complexes. Mouse RBCs also contain small amounts of  -adducin. Platelets contain - and -adducin only. Adducin functions as a barbed-end actin capping protein to regulate actin filament length and recruits spectrin to the ends of actin filaments. To further define adducin's role in vivo, we generated -adducin knockout mice. -Adducin is absent in all tissues examined in homozygous null mice. In RBCs, β- and -adducin are also absent, indicating that -adducin is the limiting subunit in tetramer formation at the spectrin-actin junction. Similarly, -adducin is absent in -null platelets. -Adducin–null mice display compensated hemolytic anemia with features characteristic of RBCs in hereditary spherocytosis (HS), including spherocytes with significant loss of surface area, decreased mean corpuscular volume (MCV), cell dehydration, and increased osmotic fragility. Platelets maintain their normal discoid shape, and bleeding times are normal. -Adducin–null mice show growth retardation at birth and throughout adulthood. Approximately 50% develop lethal communicating hydrocephalus with striking dilation of the lateral, third, and fourth ventricles. These data indicate that adducin plays a role in RBC membrane stability and in cerebrospinal fluid homeostasis.
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W. A. Anong, T. Franco, H. Chu, T. L. Weis, E. E. Devlin, D. M. Bodine, X. An, N. Mohandas, and P. S. Low
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