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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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Submitted May 12, 2008
Accepted July 25, 2008
Targeted deletion of  -adducin results in absent  - and  -adducin, compensated hemolytic anemia, and lethal hydrocephalus in mice
Raymond F. Robledo, Steven L. Ciciotte, Babette Gwynn, Kenneth E. Sahr, Diana M. Gilligan, Narla Mohandas, and Luanne L. Peters*
Physiological Genetics, The Jackson Laboratory, Bar Harbor, Maine, United States
University of Washington School of Medicine, Puget Sound Blood Center, Seattle, Washington, United States
Red Cell Physiology Laboratory, New York Blood Center, New York, New York, United States
* Corresponding author; email: luanne.peters{at}jax.org.
In the red blood cell (RBC) membrane skeleton adducin is present primarily as tetramers of  - and  -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 role in vivo, we generated -adducin knockout mice. -adducin is absent in all tissues examined in homozygous null mice. In RBCs, - 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 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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